The Metabolic Syndrome: An Overview and Proposed Mechanisms
Abstract
:1. Introduction
2. Pathophysiology of the Metabolic Syndrome
The Mechanisms of Metabolic Syndrome
3. Obesity and Cellular Energy Metabolism
3.1. Immunometabolic Influence of Adipose Tissue
3.2. Metabolic Pathway of Cellular Energy Metabolism
4. Type 2 Diabetes Mellitus
Insulin Resistance
5. Basics of Lipid Metabolism
5.1. Dyslipidaemia
5.2. Adipogenesis: From Lipid Accumulation to Hypertension
6. Hypertension
7. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
- Dominguez, L.J.; Veronese, N.; Di Bella, G.; Cusumano, C.; Parisi, A.; Tagliaferri, F.; Ciriminna, S.; Barbagallo, M. Mediterranean diet in the management and prevention of obesity. Exp. Gerontol. 2023, 174, 112121. [Google Scholar] [CrossRef] [PubMed]
- Koliaki, C.; Dalamaga, M.; Liatis, S. Update on the Obesity Epidemic: After the Sudden Rise, Is the Upward Trajectory Beginning to Flatten? Curr. Obes. Rep. 2023, 12, 514–527. [Google Scholar] [CrossRef] [PubMed]
- Dobrowolski, P.; Prejbisz, A.; Kuryłowicz, A.; Baska, A.; Burchardt, P.; Chlebus, K.; Dzida, G.; Jankowski, P.; Jaroszewicz, J.; Jaworski, P.; et al. Metabolic syndrome—A new definition and management guidelines: A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, “Club 30” Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Arch. Med. Sci. 2022, 18, 1133–1156. [Google Scholar] [CrossRef] [PubMed]
- Galluzzi, L.; Kepp, O.; Trojel-Hansen, C.; Kroemer, G. Mitochondrial Control of Cellular Life, Stress, and Death. Circ. Res. 2012, 111, 1198–1207. [Google Scholar] [CrossRef] [PubMed]
- Berg, J.M.; Tymoczko, J.L.; Stryer, L. The Citric Acid Cycle Oxidizes Two-Carbon Units. In Biochemistry; W. H. Freeman: New York, NY, USA, 2002; pp. 702–718. [Google Scholar]
- Smith, R.L.; Soeters, M.R.; Wüst, R.C.I.; Houtkooper, R.H. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr. Rev. 2018, 39, 489–517. [Google Scholar] [CrossRef] [PubMed]
- Sozen, E.; Ozer, N.K. Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review. Redox Biol. 2017, 12, 456–461. [Google Scholar] [CrossRef] [PubMed]
- Parksook, W.W.; Williams, G.H. Aldosterone and cardiovascular diseases. Cardiovasc. Res. 2022, 119, 28–44. [Google Scholar] [CrossRef] [PubMed]
- Ksiazek, S.H.; Hu, L.; Andò, S.; Pirklbauer, M.; Säemann, M.D.; Ruotolo, C.; Zaza, G.; La Manna, G.; De Nicola, L.; Mayer, G.; et al. Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic. Int. J. Mol. Sci. 2024, 25, 4035. [Google Scholar] [CrossRef] [PubMed]
- Pham, D.V.; Park, P.-H. Recent insights on modulation of inflammasomes by adipokines: A critical event for the pathogenesis of obesity and metabolism-associated diseases. Arch. Pharmacal. Res. 2020, 43, 997–1016. [Google Scholar] [CrossRef]
- Guzik, T.J.; Mangalat, D.; Korbut, R. Adipocytokines—Novel link between inflammation and vascular function? J. Physiol. Pharmacol. 2006, 57, 505–528. [Google Scholar]
- Yu, L.; Hong, W.; Lu, S.; Li, Y.; Guan, Y.; Weng, X.; Feng, Z. The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment. Front. Pharmacol. 2022, 13, 780496. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Li, L.; Zhang, Z.; Chen, P.; Shu, H.; Yang, C.; Chu, Y.; Liu, J. Ferroptosis: An important player in the inflammatory response in diabetic nephropathy. Front. Immunol. 2023, 14, 1294317. [Google Scholar] [CrossRef] [PubMed]
- Zhou, D.; Lu, P.; Mo, X.; Yang, B.; Chen, T.; Yao, Y.; Xiong, T.; Yue, L.; Yang, X. Ferroptosis and metabolic syndrome and complications: Association, mechanism, and translational applications. Front. Endocrinol. 2023, 14, 1248934. [Google Scholar] [CrossRef] [PubMed]
- McCracken, E.; Monaghan, M.; Sreenivasan, S. Pathophysiology of the metabolic syndrome. Clin. Dermatol. 2018, 36, 14–20. [Google Scholar] [CrossRef] [PubMed]
- Ambroselli, D.; Masciulli, F.; Romano, E.; Catanzaro, G.; Besharat, Z.M.; Massari, M.C.; Ferretti, E.; Migliaccio, S.; Izzo, L.; Ritieni, A.; et al. New Advances in Metabolic Syndrome, from Prevention to Treatment: The Role of Diet and Food. Nutrients 2023, 15, 640. [Google Scholar] [CrossRef] [PubMed]
- Chandrasekaran, P.; Weiskirchen, R. Cellular and Molecular Mechanisms of Insulin Resistance. Curr. Tissue Microenviron. Rep. 2024, 1, 1–12. [Google Scholar] [CrossRef]
- Codazzi, V.; Frontino, G.; Galimberti, L.; Giustina, A.; Petrelli, A. Mechanisms and risk factors of metabolic syndrome in children and adolescents. Endocrine 2024, 84, 16–28. [Google Scholar] [CrossRef] [PubMed]
- Brennan, L.; Hu, F.B. Metabolomics-Based Dietary Biomarkers in Nutritional Epidemiology—Current Status and Future Opportunities. Mol. Nutr. Food Res. 2019, 63, 1701064. [Google Scholar] [CrossRef]
- Luna-Castillo, K.P.; Olivares-Ochoa, X.C.; Hernández-Ruiz, R.G.; Llamas-Covarrubias, I.M.; Rodríguez-Reyes, S.C.; Betancourt-Núñez, A.; Vizmanos, B.; Martínez-López, E.; Muñoz-Valle, J.F.; Márquez-Sandoval, F.; et al. The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence. Nutrients 2022, 14, 1104. [Google Scholar] [CrossRef] [PubMed]
- Lin, X.; Li, H. Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front. Endocrinol. 2021, 12, 706978. [Google Scholar] [CrossRef]
- White, U.; Ravussin, E. Dynamics of adipose tissue turnover in human metabolic health and disease. Diabetologia 2019, 62, 17–23. [Google Scholar] [CrossRef] [PubMed]
- Bauer, S.; Wanninger, J.; Schmidhofer, S.; Weigert, J.; Neumeier, M.; Dorn, C.; Hellerbrand, C.; Zimara, N.; Schäffler, A.; Aslanidis, C.; et al. Sterol Regulatory Element-Binding Protein 2 (SREBP2) Activation after Excess Triglyceride Storage Induces Chemerin in Hypertrophic Adipocytes. Endocrinology 2011, 152, 26–35. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.W.; Kim, J.H.; Lee, Y.J. The Role of Adipokines in Tumor Progression and Its Association with Obesity. Biomedicines 2024, 12, 97. [Google Scholar] [CrossRef] [PubMed]
- Taheri, E.; Hosseini, S.; Qorbani, M.; Mirmiran, P. Association of adipocytokines with lipid and glycemic profiles in women with normal weight obesity. BMC Endocr. Disord. 2020, 20, 171. [Google Scholar] [CrossRef] [PubMed]
- Vilariño-García, T.; Polonio-González, M.L.; Pérez-Pérez, A.; Ribalta, J.; Arrieta, F.; Aguilar, M.; Obaya, J.C.; Gimeno-Orna, J.A.; Iglesias, P.; Navarro, J.; et al. Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes. Int. J. Mol. Sci. 2024, 25, 2338. [Google Scholar] [CrossRef] [PubMed]
- Kiernan, K.; MacIver, N.J. The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease. Front. Immunol. 2021, 11, 622468. [Google Scholar] [CrossRef] [PubMed]
- Kirichenko, T.V.; Markina, Y.V.; Bogatyreva, A.I.; Tolstik, T.V.; Varaeva, Y.R.; Starodubova, A.V. The Role of Adipokines in Inflammatory Mechanisms of Obesity. Int. J. Mol. Sci. 2022, 23, 14982. [Google Scholar] [CrossRef]
- Sahu, B.; Bal, N.C. Adipokines from white adipose tissue in regulation of whole body energy homeostasis. Biochimie 2023, 204, 92–107. [Google Scholar] [CrossRef]
- Tahergorabi, Z.; Lotfi, H.; Rezaei, M.; Aftabi, M.; Moodi, M. Crosstalk between obesity and cancer: A role for adipokines. Arch. Physiol. Biochem. 2024, 130, 155–168. [Google Scholar] [CrossRef]
- Wunderlich, C.M.; Hövelmeyer, N.; Wunderlich, F.T. Mechanisms of chronic JAK-STAT3-SOCS3 signaling in obesity. JAK-STAT 2013, 2, e23878. [Google Scholar] [CrossRef]
- Richard, A.J.; Stephens, J.M. The role of JAK-STAT signaling in adipose tissue function. Biochim. Biophys. Acta 2014, 1842, 431–439. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Y.; Zhang, Q.; Soderland, C.; Steinle, J.J. TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis. Cell. Signal. 2012, 24, 1086–1092. [Google Scholar] [CrossRef]
- Li, H.; Lin, X. Positive and negative signaling components involved in TNFalpha-induced NF-kappaB activation. Cytokine 2008, 41, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Inokuchi, J.-i. GM3 and diabetes. Glycoconj. J. 2014, 31, 193–197. [Google Scholar] [CrossRef] [PubMed]
- Sarbassov, D.D.; Guertin, D.A.; Ali, S.M.; Sabatini, D.M. Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex. Science 2005, 307, 1098–1101. [Google Scholar] [CrossRef]
- Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer. Nat. Rev. Drug Discov. 2009, 8, 627–644. [Google Scholar] [CrossRef]
- Di Zazzo, E.; Feola, A.; Zuchegna, C.; Romano, A.; Donini, C.F.; Bartollino, S.; Costagliola, C.; Frunzio, R.; Laccetti, P.; Di Domenico, M.; et al. The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility. Sci. World J. 2014, 2014, 11. [Google Scholar] [CrossRef]
- Shamsan, E.; Almezgagi, M.; Gamah, M.; Khan, N.; Qasem, A.; Chuanchuan, L.; Haining, F. The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: A comprehensive review. Front. Med. 2024, 11, 1389329. [Google Scholar] [CrossRef]
- Yang, Y.; Jia, X.; Qu, M.; Yang, X.; Fang, Y.; Ying, X.; Zhang, M.; Wei, J.; Pan, Y. Exploring the potential of treating chronic liver disease targeting the PI3K/Akt pathway and polarization mechanism of macrophages. Heliyon 2023, 9, e17116. [Google Scholar] [CrossRef]
- Wang, H.-W.; Gao, H.-L.; Wei, X.-X.; Wang, X.-H. Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway. Mol. Cell. Biochem. 2015, 407, 135–142. [Google Scholar] [CrossRef]
- Chen, C.-L.; Lin, Y.-C. Autophagy Dysregulation in Metabolic Associated Fatty Liver Disease: A New Therapeutic Target. Int. J. Mol. Sci. 2022, 23, 10055. [Google Scholar] [CrossRef] [PubMed]
- Sakers, A.; De Siqueira, M.K.; Seale, P.; Villanueva, C.J. Adipose-tissue plasticity in health and disease. Cell 2022, 185, 419–446. [Google Scholar] [CrossRef]
- Wang, L.; Liu, J.; Miao, Z.; Pan, Q.; Cao, W. Lipid droplets and their interactions with other organelles in liver diseases. Int. J. Biochem. Cell Biol. 2021, 133, 105937. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Ren, Y.; Chang, K.; Wu, W.; Griffiths, H.R.; Lu, S.; Gao, D. Adipose tissue macrophages as potential targets for obesity and metabolic diseases. Front. Immunol. 2023, 14, 1153915. [Google Scholar] [CrossRef] [PubMed]
- Röszer, T. Adipose Tissue Immunometabolism and Apoptotic Cell Clearance. Cells 2021, 10, 2288. [Google Scholar] [CrossRef] [PubMed]
- Yao, J.; Wu, D.; Qiu, Y. Adipose tissue macrophage in obesity-associated metabolic diseases. Front. Immunol. 2022, 13, 977485. [Google Scholar] [CrossRef] [PubMed]
- Liang, W.; Qi, Y.; Yi, H.; Mao, C.; Meng, Q.; Wang, H.; Zheng, C. The Roles of Adipose Tissue Macrophages in Human Disease. Front. Immunol. 2022, 13, 908749. [Google Scholar] [CrossRef] [PubMed]
- Da Cruz Nascimento, S.S.; Carvalho de Queiroz, J.L.; Fernandes de Medeiros, A.; De França Nunes, A.C.; Piuvezam, G.; Lima Maciel, B.L.; Souza Passos, T.; Morais, A.H.d.A. Anti-inflammatory agents as modulators of the inflammation in adipose tissue: A systematic review. PLoS ONE 2022, 17, e0273942. [Google Scholar] [CrossRef] [PubMed]
- Alessi, M.-C.; Juhan-Vague, I. PAI-1 and the Metabolic Syndrome: Links, Causes, and Consequences. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2200–2207. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Wang, L.; Luo, M.; Chen, N.; Deng, X.; He, J.; Zhang, L.; Luo, P.; Wu, J. Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice. Am. J. Physiol. Endocrinol. Metab. 2019, 316, E260–E267. [Google Scholar] [CrossRef]
- Fernø, J.; Strand, K.; Mellgren, G.; Stiglund, N.; Björkström, N.K. Natural Killer Cells as Sensors of Adipose Tissue Stress. Trends Endocrinol. Metab. 2020, 31, 3–12. [Google Scholar] [CrossRef]
- Litwiniuk, A.; Bik, W.; Kalisz, M.; Baranowska-Bik, A. Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 5603. [Google Scholar] [CrossRef]
- Sharma, M.; de Alba, E. Structure, Activation, and Regulation of NLRP3 and AIM2 Inflammasomes. Int. J. Mol. Sci. 2021, 22, 872. [Google Scholar] [CrossRef]
- Ye, T.; Tao, W.-Y.; Chen, X.-Y.; Jiang, C.; Di, B.; Xu, L.-L. Mechanisms of NLRP3 inflammasome activation and the development of peptide inhibitors. Cytokine Growth Factor. Rev. 2023, 74, 1–13. [Google Scholar] [CrossRef]
- Latz, E.; Xiao, T.S.; Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 2013, 13, 397–411. [Google Scholar] [CrossRef]
- Sollberger, G.; Strittmatter, G.E.; Garstkiewicz, M.; Sand, J.; Beer, H.-D. Caspase-1: The inflammasome and beyond. Innate Immun. 2014, 20, 115–125. [Google Scholar] [CrossRef]
- Zhou, R.; Yazdi, A.S.; Menu, P.; Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011, 469, 221–225. [Google Scholar] [CrossRef]
- Davis, B.K.; Wen, H.; Ting, J.P. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol. 2011, 29, 707–735. [Google Scholar] [CrossRef]
- Kim, H.K.; Chen, W.; Andreazza, A.C. The Potential Role of the NLRP3 Inflammasome as a Link between Mitochondrial Complex I Dysfunction and Inflammation in Bipolar Disorder. Neural Plast. 2015, 2015, 408136. [Google Scholar] [CrossRef]
- Chen, Y.; Ye, X.; Escames, G.; Lei, W.; Zhang, X.; Li, M.; Jing, T.; Yao, Y.; Qiu, Z.; Wang, Z.; et al. The NLRP3 inflammasome: Contributions to inflammation-related diseases. Cell Mol. Biol. Lett. 2023, 28, 51. [Google Scholar] [CrossRef]
- Pirzada, R.H.; Javaid, N.; Choi, S. The Roles of the NLRP3 Inflammasome in Neurodegenerative and Metabolic Diseases and in Relevant Advanced Therapeutic Interventions. Genes 2020, 11, 131. [Google Scholar] [CrossRef]
- Xiong, W.; Meng, X.F.; Zhang, C. NLRP3 Inflammasome in Metabolic-Associated Kidney Diseases: An Update. Front. Immunol. 2021, 12, 714340. [Google Scholar] [CrossRef]
- Sharma, B.R.; Kanneganti, T.D. NLRP3 inflammasome in cancer and metabolic diseases. Nat. Immunol. 2021, 22, 550–559. [Google Scholar] [CrossRef]
- Curley, S.; Gall, J.; Byrne, R.; Yvan-Charvet, L.; McGillicuddy, F.C. Metabolic Inflammation in Obesity—At the Crossroads between Fatty Acid and Cholesterol Metabolism. Mol. Nutr. Food Res. 2021, 65, e1900482. [Google Scholar] [CrossRef]
- Xu, Y.; Yang, Y.; Chen, X.; Jiang, D.; Zhang, F.; Guo, Y.; Hu, B.; Xu, G.; Peng, S.; Wu, L.; et al. NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors. Transl. Neurodegener. 2023, 12, 49. [Google Scholar] [CrossRef]
- Balan, A.I.; Halațiu, V.B.; Scridon, A. Oxidative Stress, Inflammation, and Mitochondrial Dysfunction: A Link between Obesity and Atrial Fibrillation. Antioxidants 2024, 13, 117. [Google Scholar] [CrossRef]
- Lehninger, A.L.; Cox, M.M.; Nelson, D.L. Lehninger Principles of Biochemistry; W.H. Freeman: New York, NY, USA, 2013. [Google Scholar]
- Zangari, J.; Petrelli, F.; Maillot, B.; Martinou, J.C. The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier. Biomolecules 2020, 10, 1068. [Google Scholar] [CrossRef]
- McCommis, K.S.; Finck, B.N. The Hepatic Mitochondrial Pyruvate Carrier as a Regulator of Systemic Metabolism and a Therapeutic Target for Treating Metabolic Disease. Biomolecules 2023, 13, 261. [Google Scholar] [CrossRef]
- Tavoulari, S.; Sichrovsky, M.; Kunji, E.R.S. Fifty years of the mitochondrial pyruvate carrier: New insights into its structure, function, and inhibition. Acta Physiol. 2023, 238, e14016. [Google Scholar] [CrossRef]
- Amelio, I.; Cutruzzolá, F.; Antonov, A.; Agostini, M.; Melino, G. Serine and glycine metabolism in cancer. Trends Biochem. Sci. 2014, 39, 191–198. [Google Scholar] [CrossRef]
- Tsouko, E.; Khan, A.S.; White, M.A.; Han, J.J.; Shi, Y.; Merchant, F.A.; Sharpe, M.A.; Xin, L.; Frigo, D.E. Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis 2014, 3, e103. [Google Scholar] [CrossRef]
- Maier, T.H. Semisynthetic production of unnatural L-α-amino acids by metabolic engineering of the cysteine-biosynthetic pathway. Nat. Biotechnol. 2003, 21, 422–427. [Google Scholar] [CrossRef]
- Lao-On, U.; Attwood, P.V.; Jitrapakdee, S. Roles of pyruvate carboxylase in human diseases: From diabetes to cancers and infection. J. Mol. Med. 2018, 96, 237–247. [Google Scholar] [CrossRef]
- Li, M.; Zhou, S.; Chen, C.; Ma, L.; Luo, D.; Tian, X.; Dong, X.; Zhou, Y.; Yang, Y.; Cui, Y. Therapeutic potential of pyruvate therapy for patients with mitochondrial diseases: A systematic review. Ther. Adv. Endocrinol. Metab. 2020, 11, 1–13. [Google Scholar] [CrossRef]
- Gray, L.R.; Tompkins, S.C.; Taylor, E.B. Regulation of pyruvate metabolism and human disease. Cell Mol. Life Sci. 2014, 71, 2577–2604. [Google Scholar] [CrossRef]
- Sugden, M.C.; Holness, M.J. The pyruvate carboxylase-pyruvate dehydrogenase axis in islet pyruvate metabolism: Going round in circles? Islets 2011, 3, 302–319. [Google Scholar] [CrossRef]
- Hughey, C.C.; Crawford, P.A. Pyruvate Carboxylase Wields a Double-Edged Metabolic Sword. Cell Metab. 2019, 29, 1236–1238. [Google Scholar] [CrossRef]
- Cappel, D.A.; Deja, S.; Duarte, J.A.G.; Kucejova, B.; Iñigo, M.; Fletcher, J.A.; Fu, X.; Berglund, E.D.; Liu, T.; Elmquist, J.K.; et al. Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. Cell Metab. 2019, 29, 1291–1305. [Google Scholar] [CrossRef]
- Yao, X.; Li, W.; Fang, D.; Xiao, C.; Wu, X.; Li, M.; Luo, Z. Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells. Adv. Sci. 2021, 8, 2100997. [Google Scholar] [CrossRef]
- Yang, W.S.; Stockwell, B.R. Ferroptosis: Death by Lipid Peroxidation. Trends Cell Biol. 2016, 26, 165–176. [Google Scholar] [CrossRef]
- Kim, J.W.; Lee, J.Y.; Oh, M.; Lee, E.W. An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis. Exp. Mol. Med. 2023, 55, 1620–1631. [Google Scholar] [CrossRef]
- Pu, F.; Chen, F.; Zhang, Z.; Shi, D.; Zhong, B.; Lv, X.; Tucker, A.B.; Fan, J.; Li, A.J.; Qin, K.; et al. Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer. Genes. Dis. 2022, 9, 347–357. [Google Scholar] [CrossRef] [PubMed]
- Luan, Y.; Griffiths, H.R. Ceramides reduce CD36 cell surface expression and oxidised LDL uptake by monocytes and macrophages. Arch. Biochem. Biophys. 2006, 450, 89–99. [Google Scholar] [CrossRef]
- Thayyullathil, F.; Cheratta, A.R.; Alakkal, A.; Subburayan, K.; Pallichankandy, S.; Hannun, Y.A.; Galadari, S. Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis. Cell Death Dis. 2021, 12, 26. [Google Scholar] [CrossRef]
- Ding, S.; Li, G.; Fu, T.; Zhang, T.; Lu, X.; Li, N.; Geng, Q. Ceramides and mitochondrial homeostasis. Cell Signal. 2024, 117, 111099. [Google Scholar] [CrossRef]
- Cheng, R.; Dhorajia, V.V.; Kim, J.; Kim, Y. Mitochondrial iron metabolism and neurodegenerative diseases. Neurotoxicology 2022, 88, 88–101. [Google Scholar] [CrossRef]
- Wang, X.; Wei, T.; Luo, J.; Lang, K.; Song, Y.; Ning, X.; Chao, Y.; Gu, Z.; Wang, L.; Chen, C.; et al. Iron Overload–Dependent Ferroptosis Aggravates LPS-Induced Acute Lung Injury by Impairing Mitochondrial Function. Inflammation 2024, 47, 1–14. [Google Scholar] [CrossRef]
- Du, Y.-x.; Zhao, Y.-t.; Sun, Y.-x.; Xu, A.-h. Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis. Mol. Med. 2023, 29, 125. [Google Scholar] [CrossRef]
- Feng, S.; Tang, D.; Wang, Y.; Li, X.; Bao, H.; Tang, C.; Dong, X.; Li, X.; Yang, Q.; Yan, Y.; et al. The mechanism of ferroptosis and its related diseases. Mol. Biomed. 2023, 4, 33. [Google Scholar] [CrossRef]
- Zhao, L.; Zhang, X.; Shen, Y.; Fang, X.; Wang, Y.; Wang, F. Obesity and iron deficiency: A quantitative meta-analysis. Obes. Rev. 2015, 16, 1081–1093. [Google Scholar] [CrossRef]
- Hutchinson, C. A review of iron studies in overweight and obese children and adolescents: A double burden in the young? Eur. J. Nutr. 2016, 55, 2179–2197. [Google Scholar] [CrossRef]
- He, L.-P.; Zhou, Z.-X.; Li, C.-P. Narrative review of ferroptosis in obesity. J. Cell Mol. Med. 2023, 27, 920–926. [Google Scholar] [CrossRef]
- Ursini, F.; Maiorino, M. Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic. Biol. Med. 2020, 152, 175–185. [Google Scholar] [CrossRef]
- Yu, W.; Liu, W.; Xie, D.; Wang, Q.; Xu, C.; Zhao, H.; Lv, J.; He, F.; Chen, B.; Yamamoto, T.; et al. High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis. Oxid. Med. Cell Longev. 2022, 2022, 9304383. [Google Scholar] [CrossRef]
- Li, Y.; Zheng, F.; Zhong, S.; Zhao, K.; Liao, H.; Liang, J.; Zheng, Q.; Wu, H.; Zhang, S.; Cao, Y.; et al. Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT. Eur. J. Pharmacol. 2024, 971, 176528. [Google Scholar] [CrossRef]
- Cui, S.; Simmons, G., Jr.; Vale, G.; Deng, Y.; Kim, J.; Kim, H.; Zhang, R.; McDonald, J.G.; Ye, J. FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids. Proc. Natl. Acad. Sci. USA 2022, 119, e2107189119. [Google Scholar] [CrossRef]
- Kraft, V.A.N.; Bezjian, C.T.; Pfeiffer, S.; Ringelstetter, L.; Müller, C.; Zandkarimi, F.; Merl-Pham, J.; Bao, X.; Anastasov, N.; Kössl, J.; et al. GTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling. ACS Cent. Sci. 2020, 6, 41–53. [Google Scholar] [CrossRef]
- Li, C.; Wu, Z.; Xue, H.; Gao, Q.; Zhang, Y.; Wang, C.; Zhao, P. Ferroptosis contributes to hypoxic-ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway. CNS Neurosci. Ther. 2022, 28, 2268–2280. [Google Scholar] [CrossRef]
- Deng, L.; He, S.; Guo, N.; Tian, W.; Zhang, W.; Luo, L. Molecular mechanisms of ferroptosis and relevance to inflammation. Inflamm. Res. 2023, 72, 281–299. [Google Scholar] [CrossRef]
- Sun, Y.; Chen, P.; Zhai, B.; Zhang, M.; Xiang, Y.; Fang, J.; Xu, S.; Gao, Y.; Chen, X.; Sui, X.; et al. The emerging role of ferroptosis in inflammation. Biomed. Pharmacother. 2020, 127, 110108. [Google Scholar] [CrossRef]
- Chen, X.; Kang, R.; Kroemer, G.; Tang, D. Ferroptosis in infection, inflammation, and immunity. J. Exp. Med. 2021, 218, 20210518. [Google Scholar] [CrossRef]
- Ueda, N.; Takasawa, K. Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease. Nutrients 2018, 10, 1173. [Google Scholar] [CrossRef] [PubMed]
- Sanches, J.M.; Zhao, L.N.; Salehi, A.; Wollheim, C.B.; Kaldis, P. Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk. FEBS J. 2023, 290, 620–648. [Google Scholar] [CrossRef]
- Li, M.; Chi, X.; Wang, Y.; Setrerrahmane, S.; Xie, W.; Xu, H. Trends in insulin resistance: Insights into mechanisms and therapeutic strategy. Signal Transduct. Target. Ther. 2022, 7, 216. [Google Scholar] [CrossRef]
- Lima, J.E.B.F.; Moreira, N.C.S.; Sakamoto-Hojo, E.T. Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2022, 874–875, 503437. [Google Scholar] [CrossRef]
- San-Millán, I. The Key Role of Mitochondrial Function in Health and Disease. Antioxidants 2023, 12, 782. [Google Scholar] [CrossRef] [PubMed]
- Brusco, N.; Sebastiani, G.; Di Giuseppe, G.; Licata, G.; Grieco, G.E.; Fignani, D.; Nigi, L.; Formichi, C.; Aiello, E.; Auddino, S.; et al. Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes. Diabetologia 2023, 66, 354–366. [Google Scholar] [CrossRef]
- Lipson, K.L.; Fonseca, S.G.; Ishigaki, S.; Nguyen, L.X.; Foss, E.; Bortell, R.; Rossini, A.A.; Urano, F. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE. Cell Metabolism 2006, 4, 245–254. [Google Scholar] [CrossRef]
- Salvadó, L.; Palomer, X.; Barroso, E.; Vázquez-Carrera, M. Targeting endoplasmic reticulum stress in insulin resistance. Trends Endocrinol. Metab. 2015, 26, 438–448. [Google Scholar] [CrossRef]
- Yuan, S.; She, D.; Jiang, S.; Deng, N.; Peng, J.; Ma, L. Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer. Mol. Med. 2024, 30, 40. [Google Scholar] [CrossRef]
- Chen, X.; Shi, C.; He, M.; Xiong, S.; Xia, X. Endoplasmic reticulum stress: Molecular mechanism and therapeutic targets. Signal Transduct. Target. Ther. 2023, 8, 352. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.-W.; Guan, B.-J.; Alzahrani, M.R.; Gao, Z.; Gao, L.; Bracey, S.; Wu, J.; Mbow, C.A.; Jobava, R.; Haataja, L.; et al. Adaptation to chronic ER stress enforces pancreatic β-cell plasticity. Nat. Commun. 2022, 13, 4621. [Google Scholar] [CrossRef]
- Zhang, J.; Guo, J.; Yang, N.; Huang, Y.; Hu, T.; Rao, C. Endoplasmic reticulum stress-mediated cell death in liver injury. Cell Death Dis. 2022, 13, 1051. [Google Scholar] [CrossRef] [PubMed]
- Panwar, V.; Singh, A.; Bhatt, M.; Tonk, R.K.; Azizov, S.; Raza, A.S.; Sengupta, S.; Kumar, D.; Garg, M. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct. Target. Ther. 2023, 8, 375. [Google Scholar] [CrossRef]
- lagosklonny, M.V. TOR-centric view on insulin resistance and diabetic complications: Perspective for endocrinologists and gerontologists. Cell Death Dis. 2013, 4, e964. [Google Scholar] [CrossRef]
- Ramasubbu, K.; Devi Rajeswari, V. Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: A perspective review. Mol. Cell Biochem. 2023, 478, 1307–1324. [Google Scholar] [CrossRef]
- Yoon, M.S. The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling. Nutrients 2017, 9, 1176. [Google Scholar] [CrossRef]
- Szwed, A.; Kim, E.; Jacinto, E. Regulation and metabolic functions of mTORC1 and mTORC. Physiol. Rev. 2021, 101, 1371–1426. [Google Scholar] [CrossRef] [PubMed]
- Mir, S.A.; Dar, A.; Alshehri, S.A.; Wahab, S.; Hamid, L.; Almoyad, M.A.A.; Ali, T.; Bader, G.N. Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer. Pharmaceuticals 2023, 16, 1004. [Google Scholar] [CrossRef] [PubMed]
- Tuo, Y.; Xiang, M. mTOR: A double-edged sword for diabetes. J. Leukoc. Biol. 2019, 106, 385–395. [Google Scholar] [CrossRef]
- Aguirre, G.A.; De Ita, J.R.; de la Garza, R.G.; Castilla-Cortazar, I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J. Transl. Med. 2016, 14, 3. [Google Scholar] [CrossRef] [PubMed]
- Clemmons, D.R. Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. Endocrinol. Metab. Clin. N. Am. 2012, 41, 425–443. [Google Scholar] [CrossRef] [PubMed]
- Clemmons, D.R. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J. Clin. Investig. 2004, 113, 25–27. [Google Scholar] [CrossRef] [PubMed]
- Müller, T.D.; Finan, B.; Bloom, S.R.; D‘Alessio, D.; Drucker, D.J.; Flatt, P.R.; Fritsche, A.; Gribble, F.; Grill, H.J.; Habener, J.F.; et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 2019, 30, 72–130. [Google Scholar] [CrossRef] [PubMed]
- Zhao, A.Z.; Zhao, H.; Teague, J.; Fujimoto, W.; Beavo, J.A. Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B. Proc. Natl. Acad. Sci. USA 1997, 94, 3223–3228. [Google Scholar] [CrossRef]
- Doyle, M.E.; Egan, J.M. Mechanisms of Action of GLP-1 in the Pancreas. Pharmacol. Ther. 2007, 113, 546–593. [Google Scholar] [CrossRef] [PubMed]
- Tengholm, A.; Gylfe, E. cAMP signalling in insulin and glucagon secretion. Diabetes Obes. Metab. 2017, 19, 42–53. [Google Scholar] [CrossRef] [PubMed]
- Kim, W.; Egan, J.M. The Role of Incretins in Glucose Homeostasis and Diabetes Treatment. Pharmacol. Rev. 2008, 60, 470–512. [Google Scholar] [CrossRef] [PubMed]
- Yabe, D.; Seino, Y. Two incretin hormones GLP-1 and GIP: Comparison of their actions in insulin secretion and beta cell preservation. Prog. Biophys. Mol. Biol. 2011, 107, 248–256. [Google Scholar] [CrossRef]
- Nadkarni, P.; Chepurny, O.G.; Holz, G.G. Regulation of glucose homeostasis by GLP-1. Prog. Mol. Biol. Transl. Sci. 2014, 121, 23–65. [Google Scholar] [CrossRef]
- Trzaskalski, N.A.; Fadzeyeva, E.; Mulvihill, E.E. Dipeptidyl Peptidase-4 at the Interface Between Inflammation and Metabolism. Clin. Med. Insights Endocrinol. Diabetes 2020, 13. [Google Scholar] [CrossRef] [PubMed]
- Lemaire, K.; Schuit, F. Integrating Insulin Secretion and ER Stress in Pancreatic [beta]-Cells. Nat. Cell Biol. 2012, 14, 979–981. [Google Scholar] [CrossRef]
- Roth, T.L.; Sweatt, J.D. Rhythms of Memory. Nat. Neurosci. 2008, 11, 993–994. [Google Scholar] [CrossRef]
- Zanassi, P.; Paolillo, M.; Feliciello, A.; Avvedimento, E.V.; Gallo, V.; Schinelli, S. cAMP-Dependent Protein Kinase Induces cAMP-Response Element-Binding Protein Phosphorylation via an Intracellular Calcium Release/ERK-Dependent Pathway in Striatal Neurons. J. Biol. Chem. 2001, 276, 11487–11495. [Google Scholar] [CrossRef]
- Sutherland, E.W.; Robison, G.A. The Role of Cyclic AMP in the Control of Carbohydrate Metabolism. Diabetes 1969, 18, 797–819. [Google Scholar] [CrossRef]
- Sassone-Corsi, P. The Cyclic AMP Pathway. Cold Spring Harb. Perspect. Biol. 2012, 4, a011148. [Google Scholar] [CrossRef] [PubMed]
- Uyttersprot, N.; Costagliola, S.; Dumont, J.E.; Miot, F. Requirement for cAMP-Response Element (CRE) Binding Protein/CRE Modulator Transcription Factors in Thyrotropin-Induced Proliferation of Dog Thyroid Cells in Primary Culture. Eur. J. Biochem. 1999, 259, 370–378. [Google Scholar] [CrossRef] [PubMed]
- Mayr, B.; Montminy, M. Transcriptional Regulation by the Phosphorylation-Dependent Factor CREB. Nat. Rev. Mol. Cell Biol. 2001, 2, 599–609. [Google Scholar] [CrossRef]
- Zhang, C.; Wang, G.; Zheng, Z.; Maddipati, K.R.; Zhang, X.; Dyson, G.; Williams, P.; Duncan, S.A.; Kaufman, R.J.; Zhang, K. Endoplasmic Reticulum-Tethered Transcription Factor cAMP Responsive Element-Binding Protein, Hepatocyte Specific, Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis Upon Metabolic Stress in Mice. Hepatology 2012, 55, 1070–1082. [Google Scholar] [CrossRef]
- Zhang, K.; Shen, X.; Wu, J.; Sakaki, K.; Saunders, T.; Rutkowski, D.T.; Back, S.H.; Kaufman, R.J. Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response. Cell 2006, 124, 587–599. [Google Scholar] [CrossRef]
- Nakagawa, Y.; Araki, M.; Han, S.I.; Mizunoe, Y.; Shimano, H. CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions. Nutrients 2021, 13, 3204. [Google Scholar] [CrossRef] [PubMed]
- Nakagawa, Y.; Shimano, H. CREBH Regulates Systemic Glucose and Lipid Metabolism. Int. J. Mol. Sci. 2018, 19, 1396. [Google Scholar] [CrossRef] [PubMed]
- Wade, H.; Pan, K.; Su, Q. CREBH: A Complex Array of Regulatory Mechanisms in Nutritional Signaling, Metabolic Inflammation, and Metabolic Disease. Mol. Nutr. Food Res. 2021, 65, 2000771. [Google Scholar] [CrossRef] [PubMed]
- Shen, S.; Shen, M.; Kuang, L.; Yang, K.; Wu, S.; Liu, X.; Wang, Y.; Wang, Y. SIRT1/SREBPs-Mediated Regulation of Lipid Metabolism. Pharmacol. Res. 2024, 199, 107037. [Google Scholar] [CrossRef]
- Clemente-Suárez, V.J.; Beltrán-Velasco, A.I.; Redondo-Flórez, L.; Martín-Rodríguez, A.; Tornero-Aguilera, J.F. Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients 2023, 15, 2749. [Google Scholar] [CrossRef]
- Zhang, R.; Liu, W.; Zeng, J.; Meng, J.; Jiang, H.; Wang, J.; Xing, D. Niemann-Pick C1-Like 1 Inhibitors for Reducing Cholesterol Absorption. Eur. J. Med. Chem. 2022, 230, 114111. [Google Scholar] [CrossRef]
- Berberich, A.J.; Hegele, R.A. A Modern Approach to Dyslipidemia. Endocr. Rev. 2021, 43, 611–653. [Google Scholar] [CrossRef]
- von Eckardstein, A.; Nordestgaard, B.G.; Remaley, A.T.; Catapano, A.L. High-Density Lipoprotein Revisited: Biological Functions and Clinical Relevance. Eur. Heart J. 2023, 44, 1394–1407. [Google Scholar] [CrossRef]
- Bhargava, S.; de la Puente-Secades, S.; Schurgers, L.; Jankowski, J. Lipids and Lipoproteins in Cardiovascular Diseases: A Classification. Trends Endocrinol. Metab. 2022, 33, 409–423. [Google Scholar] [CrossRef]
- Shen, W.J.; Azhar, S.; Kraemer, F.B. SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux. Annu. Rev. Physiol. 2018, 80, 95–116. [Google Scholar] [CrossRef]
- Behbodikhah, J.; Ahmed, S.; Elyasi, A.; Kasselman, L.J.; De Leon, J.; Glass, A.D.; Reiss, A.B. Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites 2021, 11, 690. [Google Scholar] [CrossRef] [PubMed]
- Duarte Lau, F.; Giugliano, R.P. Lipoprotein(a) and Its Significance in Cardiovascular Disease: A Review. JAMA Cardiol. 2022, 7, 760–769. [Google Scholar] [CrossRef] [PubMed]
- Possik, E.; Al-Mass, A.; Peyot, M.L.; Ahmad, R.; Al-Mulla, F.; Madiraju, S.R.M.; Prentki, M. New Mammalian Glycerol-3-Phosphate Phosphatase: Role in β-Cell, Liver and Adipocyte Metabolism. Front. Endocrinol. 2021, 12, 706607. [Google Scholar] [CrossRef] [PubMed]
- Chu, Y.D.; Chen, C.W.; Lai, M.W.; Lim, S.N.; Lin, W.R. Bioenergetic Alteration in Gastrointestinal Cancers: The Good, the Bad and the Ugly. World J. Gastroenterol. 2023, 29, 4499–4527. [Google Scholar] [CrossRef] [PubMed]
- Ammar, M.-R.; Kassas, N.; Bader, M.-F.; Vitale, N. Phosphatidic Acid in Neuronal Development: A Node for Membrane and Cytoskeleton Rearrangements. Biochimie 2014, 107 Pt A, 51–57. [Google Scholar] [CrossRef]
- Brault, J.J.; Dohm, G.L.; Houmard, J.A. Skeletal Muscle Metabolism and Obesity. In Mastering the UKCAT; Routledge: London, UK, 2015; Volume 2, p. 249. [Google Scholar]
- Tarantino, G.; Caputi, A. JNKs, Insulin Resistance and Inflammation: A Possible Link Between NAFLD and Coronary Artery Disease. World J. Gastroenterol. 2011, 17, 3785–3794. [Google Scholar] [CrossRef] [PubMed]
- Yen, C.-L.E.; Stone, S.J.; Koliwad, S.; Harris, C.; Farese, R.V. Thematic Review Series: Glycerolipids. DGAT Enzymes and Triacylglycerol Biosynthesis. J. Lipid Res. 2008, 49, 2283–2301. [Google Scholar] [CrossRef] [PubMed]
- Brindley, D.N.; Kok, B.P.C.; Kienesberger, P.C.; Lehner, R.; Dyck, J.R.B. Shedding Light on the Enigma of Myocardial Lipotoxicity: The Involvement of Known and Putative Regulators of Fatty Acid Storage and Mobilization. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E897–E908. [Google Scholar] [CrossRef] [PubMed]
- Tan, C.Y.; Vidal-Puig, A. Adipose Tissue Expandability: The Metabolic Problems of Obesity May Arise from the Inability to Become More Obese. Biochem. Soc. Trans. 2008, 36, 935–940. [Google Scholar] [CrossRef] [PubMed]
- Lafontan, M.; Langin, D. Lipolysis and Lipid Mobilization in Human Adipose Tissue. Prog. Lipid Res. 2009, 48, 275–297. [Google Scholar] [CrossRef]
- Steensels, S.; Ersoy, B.A. Fatty Acid Activation in Thermogenic Adipose Tissue. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2019, 1864, 79–90. [Google Scholar] [CrossRef] [PubMed]
- Rutkowski, J.M.; Stern, J.H.; Scherer, P.E. The Cell Biology of Fat Expansion. J. Cell Biol. 2015, 208, 501–512. [Google Scholar] [CrossRef]
- Man, K.; Kallies, A.; Vasanthakumar, A. Resident and Migratory Adipose Immune Cells Control Systemic Metabolism and Thermogenesis. Cell Mol. Immunol. 2022, 19, 421–431. [Google Scholar] [CrossRef]
- Maniyadath, B.; Zhang, Q.; Gupta, R.K.; Mandrup, S. Adipose Tissue at Single-Cell Resolution. Cell Metab. 2023, 35, 386–413. [Google Scholar] [CrossRef]
- Shamsi, F.; Zheng, R.; Ho, L.-L.; Chen, K.; Tseng, Y.-H. Comprehensive Analysis of Intercellular Communication in the Thermogenic Adipose Niche. Commun. Biol. 2023, 6, 761. [Google Scholar] [CrossRef] [PubMed]
- Blondin, D.P. Human Thermogenic Adipose Tissue. Curr. Opin. Genet. Dev. 2023, 80, 102054. [Google Scholar] [CrossRef]
- Carpentier, A.C.; Blondin, D.P.; Haman, F.; Richard, D. Brown Adipose Tissue—A Translational Perspective. Endocr. Rev. 2022, 44, 143–192. [Google Scholar] [CrossRef]
- Yuko, O.-O.; Saito, M. Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis. Diabetes Metab. J. 2021, 45, 840–852. [Google Scholar] [CrossRef] [PubMed]
- Scheele, C.; Nielsen, S. Metabolic Regulation and the Anti-Obesity Perspectives of Human Brown Fat. Redox Biol. 2017, 12, 770–775. [Google Scholar] [CrossRef] [PubMed]
- Peng, Y.; Zhao, L.; Li, M.; Liu, Y.; Shi, Y.; Zhang, J. Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis. Biomolecules 2024, 14, 483. [Google Scholar] [CrossRef]
- Ghesmati, Z.; Rashid, M.; Fayezi, S.; Gieseler, F.; Alizadeh, E.; Darabi, M. An Update on the Secretory Functions of Brown, White, and Beige Adipose Tissue: Towards Therapeutic Applications. Rev. Endocr. Metab. Disord. 2024, 25, 279–308. [Google Scholar] [CrossRef] [PubMed]
- Cheng, L.; Wang, J.; Dai, H.; Duan, Y.; An, Y.; Shi, L.; Lv, Y.; Li, H.; Wang, C.; Ma, Q. Brown and Beige Adipose Tissue: A Novel Therapeutic Strategy for Obesity and Type 2 Diabetes Mellitus. Adipocyte 2021, 10, 48–65. [Google Scholar] [CrossRef] [PubMed]
- Yau, W.W.; Wong, K.A.; Zhou, J.; Thimmukonda, N.K.; Wu, Y.; Bay, B.H.; Singh, B.K.; Yen, P.M. Chronic Cold Exposure Induces Autophagy to Promote Fatty Acid Oxidation, Mitochondrial Turnover, and Thermogenesis in Brown Adipose Tissue. iScience 2021, 24, 102434. [Google Scholar] [CrossRef]
- Bahler, L.; Molenaars, R.J.; Verberne, H.J.; Holleman, F. Role of the Autonomic Nervous System in Activation of Human Brown Adipose Tissue: A Review of the Literature. Diabetes Metab. 2015, 41, 437–445. [Google Scholar] [CrossRef] [PubMed]
- Razzoli, M.; Emmett, M.J.; Lazar, M.A.; Bartolomucci, A. β-Adrenergic Receptors Control Brown Adipose UCP-1 Tone and Cold Response without Affecting Its Circadian Rhythmicity. FASEB J. 2018, 32, 5640–5646. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Qi, Z.; Ding, S. Exercise-Induced Adipose Tissue Thermogenesis and Browning: How to Explain the Conflicting Findings? Int. J. Mol. Sci. 2022, 23, 13142. [Google Scholar] [CrossRef]
- Dong, H.; Qin, M.; Wang, P.; Li, S.; Wang, X. Regulatory Effects and Mechanisms of Exercise on Activation of Brown Adipose Tissue (BAT) and Browning of White Adipose Tissue (WAT). Adipocyte 2023, 12, 2266147. [Google Scholar] [CrossRef] [PubMed]
- Martin, A.R.; Chung, S.; Koehler, K. Is Exercise a Match for Cold Exposure? Common Molecular Framework for Adipose Tissue Browning. Int. J. Sports Med. 2020, 41, 427–442. [Google Scholar] [CrossRef]
- Yau, W.W.; Yen, P.M. Thermogenesis in Adipose Tissue Activated by Thyroid Hormone. Int. J. Mol. Sci. 2020, 21, 3020. [Google Scholar] [CrossRef]
- Johann, K.; Cremer, A.L.; Fischer, A.W.; Heine, M.; Pensado, E.R.; Resch, J.; Nock, S.; Virtue, S.; Harder, L.; Oelkrug, R. Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption. Cell Rep. 2019, 27, 3385–3400.e3383. [Google Scholar] [CrossRef]
- Kaikaew, K.; Grefhorst, A.; Visser, J.A. Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk. Front. Endocrinol. 2021, 12, 652444. [Google Scholar] [CrossRef] [PubMed]
- Malpique, R.; Gallego-Escuredo, J.M.; Sebastiani, G.; Villarroya, J.; López-Bermejo, A.; de Zegher, F.; Villarroya, F.; Ibáñez, L. Brown Adipose Tissue in Prepubertal Children: Associations with Sex, Birthweight, and Metabolic Profile. Int. J. Obes. 2019, 43, 384–391. [Google Scholar] [CrossRef] [PubMed]
- Martinez-Tellez, B.; Sanchez-Delgado, G.; Boon, M.R.; Rensen, P.C.N.; Llamas-Elvira, J.M.; Ruiz, J.R. Distribution of Brown Adipose Tissue Radiodensity in Young Adults: Implications for Cold [(18)F]FDG-PET/CT Analyses. Mol. Imaging Biol. 2020, 22, 425–433. [Google Scholar] [CrossRef] [PubMed]
- Kuryłowicz, A. Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction. Biomedicines 2023, 11, 690. [Google Scholar] [CrossRef] [PubMed]
- Cinti, S. The Endocrine Adipose Organ. Rev. Endocr. Metab. Disord. 2022, 23, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Martins, F.F.; Souza-Mello, V.; Aguila, M.B.; Mandarim-de-Lacerda, C.A. Brown Adipose Tissue as an Endocrine Organ: Updates on the Emerging Role of Batokines. Horm. Mol. Biol. Clin. Investig. 2023, 44, 219–227. [Google Scholar] [CrossRef] [PubMed]
- Luo, L.; Liu, M. Adipose Tissue in Control of Metabolism. J. Endocrinol. 2016, 231, R77–R99. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.-X. PPARs: Diverse Regulators in Energy Metabolism and Metabolic Diseases. Cell Res. 2010, 20, 124–137. [Google Scholar] [CrossRef] [PubMed]
- Hajer, G.R.; van Haeften, T.W.; Visseren, F.L.J. Adipose Tissue Dysfunction in Obesity, Diabetes, and Vascular Diseases. Eur. Heart J. 2008, 29, 2959–2971. [Google Scholar] [CrossRef]
- Bjørndal, B.; Burri, L.; Staalesen, V.; Skorve, J.; Berge, R.K. Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic Agents. J. Obesity 2011, 2011, 490650. [Google Scholar] [CrossRef]
- Christodoulides, C.; Vidal-Puig, A. PPARs and Adipocyte Function. Mol. Cell. Endocrinol. 2010, 318, 61–68. [Google Scholar] [CrossRef] [PubMed]
- Stino, A.M.; Rumora, A.E.; Kim, B.; Feldman, E.L. Evolving Concepts on the Role of Dyslipidemia, Bioenergetics, and Inflammation in the Pathogenesis and Treatment of Diabetic Peripheral Neuropathy. J. Peripher. Nerv. Syst. 2020, 25, 76–84. [Google Scholar] [CrossRef] [PubMed]
- Zhao, P.; Zhao, Z.; Yu, Z.; Chen, L.; Jin, Y.; Wu, J.; Ren, Z. Application of Synthetic Lipid Droplets in Metabolic Diseases. Clin. Transl. Med. 2023, 13, e1441. [Google Scholar] [CrossRef]
- Chandel, N.S. Lipid Metabolism. Cold Spring Harb. Perspect. Biol. 2021, 13, a040576. [Google Scholar] [CrossRef]
- Szrok-Jurga, S.; Czumaj, A.; Turyn, J.; Hebanowska, A.; Swierczynski, J.; Sledzinski, T.; Stelmanska, E. The Physiological and Pathological Role of Acyl-CoA Oxidation. Int. J. Mol. Sci. 2023, 24, 14857. [Google Scholar] [CrossRef]
- Zadoorian, A.; Du, X.; Yang, H. Lipid Droplet Biogenesis and Functions in Health and Disease. Nat. Rev. Endocrinol. 2023, 19, 443–459. [Google Scholar] [CrossRef] [PubMed]
- Memon, R.A.; Fuller, J.; Moser, A.H.; Smith, P.J. Regulation of Putative Fatty Acid Transporters and Acyl-CoA Synthetase in Liver and Adipose Tissue in ob/ob Mice. Diabetes 1999, 48, 121–127. [Google Scholar] [CrossRef]
- Viscarra, J.A.; Ortiz, R.M. Cellular Mechanisms Regulating Fuel Metabolism in Mammals: Role of Adipose Tissue and Lipids During Prolonged Food Deprivation. Metabolism 2013, 62, 889–897. [Google Scholar] [CrossRef] [PubMed]
- Grevengoed, T.J.; Klett, E.L.; Coleman, R.A. Acyl-CoA Metabolism and Partitioning. Annu. Rev. Nutr. 2014, 34, 1–30. [Google Scholar] [CrossRef]
- Ellis, J.M.; Bowman, C.E.; Wolfgang, M.J. Metabolic and Tissue-Specific Regulation of Acyl-CoA Metabolism. PLoS ONE 2015, 10, e0116587. [Google Scholar] [CrossRef]
- Virmani, M.A.; Cirulli, M. The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation. Int. J. Mol. Sci. 2022, 23, 2717. [Google Scholar] [CrossRef]
- Brock, M. Role of Cellular Control of Propionyl-CoA Levels for Microbial Pathogenesis. In Handbook of Hydrocarbon and Lipid Microbiology; Timmis, K., Ed.; Springer: Berlin/Heidelberg, Germany, 2010; pp. 3279–3291. [Google Scholar] [CrossRef]
- Rush, E.C.; Katre, P.; Yajnik, C.S. Vitamin B12: One Carbon Metabolism, Fetal Growth and Programming for Chronic Disease. Eur. J. Clin. Nutr. 2014, 68, 2–7. [Google Scholar] [CrossRef]
- Newgard, C.B. Interplay Between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance. Cell Metab. 2012, 15, 606–614. [Google Scholar] [CrossRef]
- Newgard, C.B.; An, J.; Bain, J.R.; Muehlbauer, M.J.; Stevens, R.D.; Lien, L.F.; Haqq, A.M.; Shah, S.H.; Arlotto, M.; Slentz, C.A. A Branched-Chain Amino Acid-Related Metabolic Signature That Differentiates Obese and Lean Humans and Contributes to Insulin Resistance. Cell Metab. 2009, 9, 311–326. [Google Scholar] [CrossRef]
- Wongkittichote, P.; Ah Mew, N.; Chapman, K.A. Propionyl-CoA Carboxylase—A Review. Mol. Genet. Metab. 2017, 122, 145–152. [Google Scholar] [CrossRef]
- Listenberger, L.L.; Ory, D.S.; Schaffer, J.E. Palmitate-Induced Apoptosis Can Occur Through a Ceramide-Independent Pathway. J. Biol. Chem. 2001, 276, 14890–14895. [Google Scholar] [CrossRef]
- Jung, I.-R.; Choi, S.-E.; Jung, J.-G.; Lee, S.-A.; Han, S.J.; Kim, H.J.; Kim, D.J.; Lee, K.-W.; Kang, Y. Involvement of Iron Depletion in Palmitate-Induced Lipotoxicity of Beta Cells. Mol. Cell Endocrinol. 2015, 407, 74–84. [Google Scholar] [CrossRef]
- Hovsepyan, M.; Sargsyan, E.; Bergsten, P. Palmitate-Induced Changes in Protein Expression of Insulin Secreting INS-1E Cells. J. Proteom. 2010, 73, 1148–1155. [Google Scholar] [CrossRef]
- Kwon, B.; Lee, H.-K.; Querfurth, H.W. Oleate Prevents Palmitate-Induced Mitochondrial Dysfunction, Insulin Resistance and Inflammatory Signaling in Neuronal Cells. Biochim. Biophys. Acta Mol. Cell Res. 2014, 1843, 1402–1413. [Google Scholar] [CrossRef]
- Salvado, L.; Coll, T.; Gomez-Foix, A.M.; Salmeron, E.; Barroso, E.; Palomer, X.; Vazquez-Carrera, M. Oleate Prevents Saturated-Fatty-Acid-Induced ER Stress, Inflammation and Insulin Resistance in Skeletal Muscle Cells Through an AMPK-Dependent Mechanism. Diabetologia 2013, 56, 1372–1382. [Google Scholar] [CrossRef]
- Akazawa, Y.; Cazanave, S.; Mott, J.L.; Elmi, N.; Bronk, S.F.; Kohno, S.; Charlton, M.R.; Gores, G.J. Palmitoleate Attenuates Palmitate-Induced Bim and PUMA Up-Regulation and Hepatocyte Lipoapoptosis. J. Hepatol. 2010, 52, 586–593. [Google Scholar] [CrossRef]
- Hiltunen, J.K.; Autio, K.J.; Schonauer, M.S.; Kursu, V.A.S.; Dieckmann, C.L.; Kastaniotis, A.J. Mitochondrial Fatty Acid Synthesis and Respiration. Biochim. Biophys. Acta Bioenerg. 2010, 1797, 1195–1202. [Google Scholar] [CrossRef]
- Berg, J.M.; Tymoczko, J.L.; Stryer, L. Fatty Acids Are Synthesized and Degraded by Different Pathways. In Biochemistry; W. H. Freeman: New York, NY, USA, 2002; pp. 920–933. [Google Scholar]
- Li, X.; Bi, X. Integrated Control of Fatty Acid Metabolism in Heart Failure. Metabolites 2023, 13, 615. [Google Scholar] [CrossRef]
- Fillmore, N.; Lopaschuk, G.D. Malonyl CoA: A Promising Target for the Treatment of Cardiac Disease. IUBMB Life 2014, 66, 139–146. [Google Scholar] [CrossRef]
- Summers, S.A. Ceramides in Insulin Resistance and Lipotoxicity. Prog. Lipid Res. 2006, 45, 42–72. [Google Scholar] [CrossRef]
- Chavez, J.A.; Summers, S.A. A Ceramide-Centric View of Insulin Resistance. Cell Metab. 2012, 15, 585–594. [Google Scholar] [CrossRef]
- Hait, N.C.; Maiti, A. The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer. Mediat. Inflamm. 2017, 2017, 4806541. [Google Scholar] [CrossRef]
- Leu, S.; Tsang, Y.; Ho, L.; Yang, C.; Shao, A.; Chang, C.; Lin, H.; Tsai, P.; Sung, J.; Tsai, Y. NLRP3 Inflammasome Activation, Metabolic Danger Signals, and Protein Binding Partners. J. Endocrinol. 2023, 257, e220184. [Google Scholar] [CrossRef]
- Bismuth, J.; Lin, P.; Yao, Q.; Chen, C. Ceramide: A Common Pathway for Atherosclerosis? Atherosclerosis 2008, 196, 497–504. [Google Scholar] [CrossRef]
- Niaudet, C.; Bonnaud, S.; Guillonneau, M.; Gouard, S.; Gaugler, M.-H.; Dutoit, S.; Ripoche, N.; Dubois, N.; Trichet, V.; Corre, I.; et al. Plasma Membrane Reorganization Links Acid Sphingomyelinase/Ceramide to p38 MAPK Pathways in Endothelial Cells Apoptosis. Cell Signal. 2017, 33, 10–21. [Google Scholar] [CrossRef]
- Håversen, L.; Danielsson, K.N.; Fogelstrand, L.; Wiklund, O. Induction of Proinflammatory Cytokines by Long-Chain Saturated Fatty Acids in Human Macrophages. Atherosclerosis 2009, 202, 382–393. [Google Scholar] [CrossRef]
- Novgorodov, S.A.; Wu, B.X.; Gudz, T.I.; Bielawski, J.; Ovchinnikova, T.V.; Hannun, Y.A.; Obeid, L.M. Novel Pathway of Ceramide Production in Mitochondria: Thioesterase and Neutral Ceramidase Produce Ceramide from Sphingosine and Acyl-CoA. J. Biol. Chem. 2011, 286, 25352–25362. [Google Scholar] [CrossRef]
- Potenza, M.A.; Gagliardi, S.; Nacci, C.; Carratu, M.R.; Montagnani, M. Endothelial Dysfunction in Diabetes: From Mechanisms to Therapeutic Targets. Curr. Med. Chem. 2009, 16, 94–112. [Google Scholar] [CrossRef]
- Baffi, T.R.; Newton, A.C. mTOR Regulation of AGC Kinases: New Twist to an Old Tail. Mol. Pharmacol. 2022, 101, 213–218. [Google Scholar] [CrossRef]
- Kitagishi, Y.; Kobayashi, M.; Kikuta, K.; Matsuda, S. Roles of PI3K/AKT/GSK3/mTOR Pathway in Cell Signaling of Mental Illnesses. Depress. Res. Treat. 2012, 2012, 752563. [Google Scholar] [CrossRef]
- Dimmeler, S.; Fleming, I.; Fisslthaler, B.; Hermann, C.; Busse, R.; Zeiher, A.M. Activation of Nitric Oxide Synthase in Endothelial Cells by Akt-Dependent Phosphorylation. Nature 1999, 399, 601–605. [Google Scholar] [CrossRef]
- Hao, K.; Wang, J.; Yu, H.; Chen, L.; Zeng, W.; Wang, Z.; Hu, G. Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy. PPAR Res. 2023, 2023, 6422804. [Google Scholar] [CrossRef]
- Barbier, O.; Torra, I.P.; Duguay, Y.; Blanquart, C.; Fruchart, J.-C.; Glineur, C.; Staels, B. Pleiotropic Actions of Peroxisome Proliferator–Activated Receptors in Lipid Metabolism and Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 717–726. [Google Scholar] [CrossRef]
- Moschen, A.R.; Tilg, H. Adipocytokines: Mediators Linking Adipose Tissue, Inflammation and Immunity. Nat. Rev. Immunol. 2006, 6, 772–783. [Google Scholar] [CrossRef]
- Guerre-Millo, M. Adiponectin: An Update. Diabetes Metab. 2008, 34, 12–18. [Google Scholar] [CrossRef]
- Roy, B.; Palaniyandi, S.S. Tissue-Specific Role and Associated Downstream Signaling Pathways of Adiponectin. Cell Biosci. 2021, 11, 77. [Google Scholar] [CrossRef] [PubMed]
- Steinberg, G.R.; Carling, D. AMP-Activated Protein Kinase: The Current Landscape for Drug Development. Nat. Rev. Drug Discov. 2019, 18, 527–551. [Google Scholar] [CrossRef] [PubMed]
- Rey, V.; Tamargo-Gómez, I. From Kinases to Diseases: Investigating the Role of AMPK in Human Pathologies. Kinases Phosphatases 2023, 1, 181–205. [Google Scholar] [CrossRef]
- Sharma, A.; Anand, S.K.; Singh, N.; Dwivedi, U.N.; Kakkar, P. AMP-Activated Protein Kinase: An Energy Sensor and Survival Mechanism in the Reinstatement of Metabolic Homeostasis. Exp. Cell Res. 2023, 428, 113614. [Google Scholar] [CrossRef] [PubMed]
- Kadowaki, T.; Yamauchi, T.; Kubota, N.; Hara, K.; Ueki, K.; Tobe, K. Adiponectin and Adiponectin Receptors in Insulin Resistance, Diabetes, and the Metabolic Syndrome. J. Clin. Investig. 2006, 116, 1784–1792. [Google Scholar] [CrossRef]
- Antuna-Puente, B.; Feve, B.; Fellahi, S.; Bastard, J.-P. Adipokines: The Missing Link Between Insulin Resistance and Obesity. Diabetes Metab. 2008, 34, 2–11. [Google Scholar] [CrossRef]
- Ruderman, N.B.; Xu, X.J.; Nelson, L.; Cacicedo, J.M.; Saha, A.K.; Lan, F.; Ido, Y. AMPK and SIRT1: A Long-Standing Partnership? Am. J. Physiol. Endocrinol. Metab. 2010, 298, E751–E760. [Google Scholar] [CrossRef]
- Kosgei, V.J.; Coelho, D.; Guéant-Rodriguez, R.M.; Guéant, J.L. Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism. Cells 2020, 9, 1882. [Google Scholar] [CrossRef] [PubMed]
- Abu Shelbayeh, O.; Arroum, T.; Morris, S.; Busch, K.B. PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response. Antioxidants 2023, 12, 1075. [Google Scholar] [CrossRef]
- Chand, S.; Tripathi, A.S.; Dewani, A.P.; Sheikh, N.W.A. Molecular Targets for Management of Diabetes: Remodelling of White Adipose to Brown Adipose Tissue. Life Sci. 2024, 345, 122607. [Google Scholar] [CrossRef]
- Chen, Z.; Yang, L.; Liu, Y.; Huang, P.; Song, H.; Zheng, P. The Potential Function and Clinical Application of FGF21 in Metabolic Diseases. Front. Pharmacol. 2022, 13, 1089214. [Google Scholar] [CrossRef] [PubMed]
- Salminen, A.; Kauppinen, A.; Kaarniranta, K. FGF21 Activates AMPK Signaling: Impact on Metabolic Regulation and the Aging Process. J. Mol. Med. 2017, 95, 123–131. [Google Scholar] [CrossRef] [PubMed]
- Sun, C.; Mao, S.; Chen, S.; Zhang, W.; Liu, C. PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue. Int. J. Mol. Sci. 2021, 22, 8974. [Google Scholar] [CrossRef] [PubMed]
- Hong, F.; Pan, S.; Guo, Y.; Xu, P.; Zhai, Y. PPARs as Nuclear Receptors for Nutrient and Energy Metabolism. Molecules 2019, 24, 2545. [Google Scholar] [CrossRef] [PubMed]
- Fuior, E.V.; Zvintzou, E.; Filippatos, T.; Giannatou, K.; Mparnia, V.; Simionescu, M.; Gafencu, A.V.; Kypreos, K.E. Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease. Biomedicines 2023, 11, 2696. [Google Scholar] [CrossRef] [PubMed]
- Barish, G.D.; Narkar, V.A.; Evans, R.M. PPARδ: A Dagger in the Heart of the Metabolic Syndrome. J. Clin. Investig. 2006, 116, 590–597. [Google Scholar] [CrossRef]
- Szkudelski, T.; Szkudelska, K. The Relevance of AMP-Activated Protein Kinase in Insulin-Secreting β Cells: A Potential Target for Improving β Cell Function? J. Physiol. Biochem. 2019, 75, 423–432. [Google Scholar] [CrossRef]
- Entezari, M.; Hashemi, D.; Taheriazam, A.; Zabolian, A.; Mohammadi, S.; Fakhri, F.; Hashemi, M.; Hushmandi, K.; Ashrafizadeh, M.; Zarrabi, A.; et al. AMPK Signaling in Diabetes Mellitus, Insulin Resistance and Diabetic Complications: A Pre-Clinical and Clinical Investigation. Biomed. Pharmacother. 2022, 146, 112563. [Google Scholar] [CrossRef] [PubMed]
- Peng, Z.; Chen, L.; Wang, M.; Yue, X.; Wei, H.; Xu, F.; Hou, W.; Li, Y. SREBP Inhibitors: An Updated Patent Review for 2008-Present. Expert Opin. Ther. Pat. 2023, 33, 669–680. [Google Scholar] [CrossRef]
- Li, N.; Li, X.; Ding, Y.; Liu, X.; Diggle, K.; Kisseleva, T.; Brenner, D.A. SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies. Biomedicines 2023, 11, 3280. [Google Scholar] [CrossRef]
- Uehara, K.; Santoleri, D.; Whitlock, A.E.G.; Titchenell, P.M. Insulin Regulation of Hepatic Lipid Homeostasis. Compr. Physiol. 2023, 13, 4785–4809. [Google Scholar] [CrossRef]
- Anggreini, P.; Kuncoro, H.; Sumiwi, S.A.; Levita, J. Role of the AMPK/SIRT1 Pathway in Non-Alcoholic Fatty Liver Disease (Review). Mol. Med. Rep. 2023, 27, 12922. [Google Scholar] [CrossRef]
- Chen, C.; Kassan, A.; Castañeda, D.; Gabani, M.; Choi, S.K.; Kassan, M. Metformin Prevents Vascular Damage in Hypertension Through the AMPK/ER Stress Pathway. Hypertens. Res. 2019, 42, 960–969. [Google Scholar] [CrossRef]
- Sepúlveda-Fragoso, V.; Alexandre-Santos, B.; Salles, A.C.P.; Proença, A.B.; de Paula Alves, A.P.; Vázquez-Carrera, M.; Nóbrega, A.C.L.; Frantz, E.D.C.; Magliano, D.A.C. Crosstalk Between the Renin-Angiotensin System and the Endoplasmic Reticulum Stress in the Cardiovascular System: Lessons Learned So Far. Life Sci. 2021, 284, 119919. [Google Scholar] [CrossRef]
- Zhao, Q.; Song, P.; Zou, M.-H. AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling. Front. Cell Dev. Biol. 2021, 9, 691585. [Google Scholar] [CrossRef]
- Moral-Sanz, J.; Lewis, S.A.; MacMillan, S.; Ross, F.A.; Thomson, A.; Viollet, B.; Foretz, M.; Moran, C.; Hardie, D.G.; Evans, A.M. The LKB1-AMPK-α1 Signaling Pathway Triggers Hypoxic Pulmonary Vasoconstriction Downstream of Mitochondria. Sci. Signal. 2018, 11, eaau0296. [Google Scholar] [CrossRef]
- Moral-Sanz, J.; Lewis, S.A.; MacMillan, S.; Meloni, M.; McClafferty, H.; Viollet, B.; Foretz, M.; del-Pozo, J.; Evans, A.M. AMPK Deficiency in Smooth Muscles Causes Persistent Pulmonary Hypertension of the New-born and Premature Death. Nat. Commun. 2022, 13, 5034. [Google Scholar] [CrossRef]
- Flores, K.; Siques, P.; Brito, J.; Arribas, S.M. AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension. Int. J. Mol. Sci. 2022, 23, 6205. [Google Scholar] [CrossRef]
- Florance, I.; Ramasubbu, S. Current Understanding on the Role of Lipids in Macrophages and Associated Diseases. Int. J. Mol. Sci. 2022, 24, 589. [Google Scholar] [CrossRef] [PubMed]
- Wang, T.; Zhao, Y.; You, Z.; Li, X.; Xiong, M.; Li, H.; Yan, N. Endoplasmic Reticulum Stress Affects Cholesterol Homeostasis by Inhibiting LXRα Expression in Hepatocytes and Macrophages. Nutrients 2020, 12, 3088. [Google Scholar] [CrossRef] [PubMed]
- Capponi, A.M. The Control by Angiotensin II of Cholesterol Supply for Aldosterone Biosynthesis. Mol. Cell Endocrinol. 2004, 217, 113–118. [Google Scholar] [CrossRef]
- Otsuka, H.; Abe, M.; Kobayashi, H. The Effect of Aldosterone on Cardiorenal and Metabolic Systems. Int. J. Mol. Sci. 2023, 24, 5370. [Google Scholar] [CrossRef] [PubMed]
- Tomaschitz, A.; Pilz, S.; Ritz, E.; Obermayer-Pietsch, B.; Pieber, T.R. Aldosterone and Arterial Hypertension. Nat. Rev. Endocrinol. 2010, 6, 83–93. [Google Scholar] [CrossRef]
- Li, X.; Jiang, O.; Wang, S. Molecular Mechanisms of Cellular Metabolic Homeostasis in Stem Cells. Int. J. Oral. Sci. 2023, 15, 52. [Google Scholar] [CrossRef]
- Ma, J.; Li, Y.; Yang, X.; Liu, K.; Zhang, X.; Zuo, X.; Ye, R.; Wang, Z.; Shi, R.; Meng, Q.; et al. Signaling Pathways in Vascular Function and Hypertension: Molecular Mechanisms and Therapeutic Interventions. Signal Transduct. Target. Ther. 2023, 8, 168. [Google Scholar] [CrossRef]
- Kulovic-Sissawo, A.; Tocantins, C.; Diniz, M.S.; Weiss, E.; Steiner, A.; Tokic, S.; Madreiter-Sokolowski, C.T.; Pereira, S.P.; Hiden, U. Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells. Biology 2024, 13, 70. [Google Scholar] [CrossRef]
- Li, Z.; Wang, L.; Ren, Y.; Huang, Y.; Liu, W.; Lv, Z.; Qian, L.; Yu, Y.; Xiong, Y. Arginase: Shedding Light on the Mechanisms and Opportunities in Cardiovascular Diseases. Cell Death Discov. 2022, 8, 413. [Google Scholar] [CrossRef]
- Thomas, D.D. Breathing New Life into Nitric Oxide Signaling: A Brief Overview of the Interplay between Oxygen and Nitric Oxide. Redox Biol. 2015, 5, 225–233. [Google Scholar] [CrossRef]
- Tengan, C.H.; Rodrigues, G.S.; Godinho, R.O. Nitric Oxide in Skeletal Muscle: Role on Mitochondrial Biogenesis and Function. Int. J. Mol. Sci. 2012, 13, 17160–17184. [Google Scholar] [CrossRef] [PubMed]
- McCarthy, O.; Moser, O.; Eckstein, M.L.; Bain, S.C.; Pitt, J.; Bracken, R. Supplementary Nitric Oxide Donors and Exercise as Potential Means to Improve Vascular Health in People with Type 1 Diabetes: Yes to NO? Nutrients 2019, 11, 1571. [Google Scholar] [CrossRef] [PubMed]
- Blomberg, M.R.A.; Ädelroth, P. Reduction of Nitric Oxide to Nitrous Oxide in Flavodiiron Proteins: Catalytic Mechanism and Plausible Intermediates. ACS Catal. 2023, 13, 2025–2038. [Google Scholar] [CrossRef]
- Feng, C. Mechanism of Nitric Oxide Synthase Regulation: Electron Transfer and Interdomain Interactions. Coord. Chem. Rev. 2012, 256, 393–411. [Google Scholar] [CrossRef] [PubMed]
- Crabtree, M.J.; Channon, K.M. Synthesis and Recycling of Tetrahydrobiopterin in Endothelial Function and Vascular Disease. Nitric Oxide 2011, 25, 81–88. [Google Scholar] [CrossRef] [PubMed]
- Lubos, E.; Handy, D.E.; Loscalzo, J. Role of Oxidative Stress and Nitric Oxide in Atherothrombosis. Front. Biosci. 2008, 13, 5323–5344. [Google Scholar] [CrossRef] [PubMed]
- Gebhart, V.; Reiß, K.; Kollau, A.; Mayer, B.; Gorren, A.C.F. Site and Mechanism of Uncoupling of Nitric-Oxide Synthase: Uncoupling by Monomerization and Other Misconceptions. Nitric Oxide 2019, 89, 14–21. [Google Scholar] [CrossRef]
- Sullivan, J.C.; Pollock, J.S. Coupled and Uncoupled NOS: Separate but Equal? Uncoupled NOS in Endothelial Cells is a Critical Pathway for Intracellular Signaling. Circ. Res. 2006, 98, 717–719. [Google Scholar] [CrossRef]
- Siddhanta, U.; Presta, A.; Fan, B.; Wolan, D.; Rousseau, D.L.; Stuehr, D.J. Domain Swapping in Inducible Nitric-Oxide Synthase: Electron Transfer Occurs between Flavin and Heme Groups Located on Adjacent Subunits in the Dimer. J. Biol. Chem. 1998, 273, 18950–18958. [Google Scholar] [CrossRef] [PubMed]
- Gwozdzinski, K.; Pieniazek, A.; Gwozdzinski, L. Reactive Oxygen Species and Their Involvement in Red Blood Cell Damage in Chronic Kidney Disease. Oxid. Med. Cell. Longev. 2021, 2021, 6639199. [Google Scholar] [CrossRef]
- Bulmer, A.C.; Bakrania, B.; De Toit, E.F.; Boon, A.-C.; Clark, P.J.; Powell, L.W.; Wagner, K.-H.; Headrick, J.P. Bilirubin Acts as a Multipotent Guardian of Cardiovascular Integrity: More than Just a Radical Idea. Am. J. Physiol. Heart Circ. Physiol. 2018, 315, H429–H447. [Google Scholar] [CrossRef]
- Drummond, G.R.; Sobey, C.G. Endothelial NADPH Oxidases: Which NOX to Target in Vascular Disease? Trends Endocrinol. Metab. 2014, 25, 452–463. [Google Scholar] [CrossRef]
- Savoia, C.; Schiffrin, E. Reduction of C-Reactive Protein and the Use of Anti-Hypertensives. Vasc. Health Risk Manag. 2007, 3, 975–983. [Google Scholar]
- Kostov, K. The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation. Life 2021, 11, 986. [Google Scholar] [CrossRef]
- Colliva, A.; Braga, L.; Giacca, M.; Zacchigna, S. Endothelial-Cardiomyocyte Cross-Talk in Heart Development and Disease. J. Physiol. 2019, 598, 2923–2939. [Google Scholar] [CrossRef]
- Lekli, I.; Szabo, G.; Juhasz, B.; Das, S.; Das, M.; Varga, E.; Szendrei, L.; Gesztelyi, R.; Varadi, J.; Bak, I.; et al. Protective Mechanisms of Resveratrol against Ischemia-Reperfusion-Induced Damage in Hearts Obtained from Zucker Obese Rats: The Role of GLUT-4 and Endothelin. Am. J. Physiol. Heart Circ. Physiol. 2008, 294, H859–H866. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Thomaz, F.S.; John, O.D.; Sinha, P.; Shafie, S.R.; Worrall, S. The Metabolic Syndrome: An Overview and Proposed Mechanisms. Obesities 2024, 4, 226-255. https://doi.org/10.3390/obesities4030020
Thomaz FS, John OD, Sinha P, Shafie SR, Worrall S. The Metabolic Syndrome: An Overview and Proposed Mechanisms. Obesities. 2024; 4(3):226-255. https://doi.org/10.3390/obesities4030020
Chicago/Turabian StyleThomaz, Fernanda Santos, Oliver Dean John, Payel Sinha, Siti Raihanah Shafie, and Simon Worrall. 2024. "The Metabolic Syndrome: An Overview and Proposed Mechanisms" Obesities 4, no. 3: 226-255. https://doi.org/10.3390/obesities4030020