Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids
Abstract
:1. Introduction
2. Results
2.1. Concentration- and Time-Dependent Inhibition of Microglia Viability by PA
2.2. PA Induced Microglia Cell Death
2.3. FFAR Antagonists Did Not Ameliorate PA Lipotoxicity
2.4. Inhibition of Fatty Acid Uptake Ameliorated PA Lipotoxicity
2.5. Unsaturated Fatty Acids Abolished PA-Induced Decrease in Microglia Viability
2.6. Differential Effects of FFAs on Fatty Acid Uptake in BSA- and PA-Treated Cells
2.7. Differential Effects of FFAs on Incorporation of BODIPYTM FL C12 into and Accumulation of Neutral Lipids
2.8. UFAs Enhanced Neutral Lipid Staining in PA-Treated Cells
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Preparation of Fatty Acids
4.3. MTT Assay
4.4. TUNEL Assay
4.5. Annexin V Assay
4.6. Lactate Dehydrogenase (LDH) Assay
4.7. Cell Cycle Analysis
4.8. RNA Isolation
4.9. Semi-Quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) Assay
4.10. Analysis of the Effects of FFA Overload on Fatty Acid Uptake by Flow Cytometry
4.11. Analysis of the Effects of FFAs on Neutral Lipid Contents by Flow Cytometry
4.12. Visualization of Fatty Acid Uptake and Neutral Lipid Accumulation Using Confocal Microscopy
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Hussain, G.; Schmitt, F.; Loeffler, J.P.; de Aguilar, J.L. Fatting the brain: A brief of recent research. Front. Cell. Neurosci. 2013, 7, 144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Engin, A.B. What Is Lipotoxicity? Adv. Exp. Med. Biol. 2017, 960, 197–220. [Google Scholar] [CrossRef] [PubMed]
- Karmi, A.; Iozzo, P.; Viljanen, A.; Hirvonen, J.; Fielding, B.A.; Virtanen, K.; Oikonen, V.; Kemppainen, J.; Viljanen, T.; Guiducci, L.; et al. Increased brain fatty acid uptake in metabolic syndrome. Diabetes 2010, 59, 2171–2177. [Google Scholar] [CrossRef] [Green Version]
- Quehenberger, O.; Armando, A.M.; Brown, A.H.; Milne, S.B.; Myers, D.S.; Merrill, A.H.; Bandyopadhyay, S.; Jones, K.N.; Kelly, S.; Shaner, R.L.; et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J. Lipid Res. 2010, 51, 3299–3305. [Google Scholar] [CrossRef] [Green Version]
- Carta, G.; Murru, E.; Lisai, S.; Sirigu, A.; Piras, A.; Collu, M.; Batetta, B.; Gambelli, L.; Banni, S. Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels of N-acylethanolamides in rat tissues. PLoS ONE 2015, 10, e0120424. [Google Scholar] [CrossRef] [Green Version]
- Melo, H.M.; Seixas da Silva, G.D.S.; Sant’Ana, M.R.; Teixeira, C.V.L.; Clarke, J.R.; Miya Coreixas, V.S.; de Melo, B.C.; Fortuna, J.T.S.; Forny-Germano, L.; Ledo, J.H.; et al. Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-alpha. Cell Rep. 2020, 30, 2180–2194.e8. [Google Scholar] [CrossRef] [Green Version]
- Dragano, N.R.; Monfort-Pires, M.; Velloso, L.A. Mechanisms Mediating the Actions of Fatty Acids in the Hypothalamus. Neuroscience 2020, 447, 15–27. [Google Scholar] [CrossRef]
- Firlag, M.; Kamaszewski, M.; Gaca, K.; Adamek, D.; Balasinska, B. The neuroprotective effect of long-term n-3 polyunsaturated fatty acids supplementation in the cerebral cortex and hippocampus of aging rats. Folia Neuropathol. 2013, 51, 235–242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jia, D.; Heng, L.J.; Yang, R.H.; Gao, G.D. Fish oil improves learning impairments of diabetic rats by blocking PI3K/AKT/nuclear factor-kappaB-mediated inflammatory pathways. Neuroscience 2014, 258, 228–237. [Google Scholar] [CrossRef] [PubMed]
- Mancini, A.D.; Poitout, V. The fatty acid receptor FFA1/GPR40 a decade later: How much do we know? Trends Endocrinol. Metab. TEM 2013, 24, 398–407. [Google Scholar] [CrossRef]
- Zhou, Y.J.; Song, Y.L.; Zhou, H.; Li, Y. Linoleic acid activates GPR40/FFA1 and phospholipase C to increase [Ca2+]i release and insulin secretion in islet beta-cells. Chin. Med. Sci. J. 2012, 27, 18–23. [Google Scholar] [CrossRef]
- Kim, J.Y.; Lee, H.J.; Lee, S.J.; Jung, Y.H.; Yoo, D.Y.; Hwang, I.K.; Seong, J.K.; Ryu, J.M.; Han, H.J. Palmitic Acid-BSA enhances Amyloid-beta production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1alpha and Akt/NF-kappaB pathways. Sci. Rep. 2017, 7, 4335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milligan, G.; Alvarez-Curto, E.; Hudson, B.D.; Prihandoko, R.; Tobin, A.B. FFA4/GPR120: Pharmacology and Therapeutic Opportunities. Trends Pharmacol. Sci. 2017, 38, 809–821. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kimura, I.; Ichimura, A.; Ohue-Kitano, R.; Igarashi, M. Free Fatty Acid Receptors in Health and Disease. Physiol. Rev. 2020, 100, 171–210. [Google Scholar] [CrossRef] [PubMed]
- Ohue-Kitano, R.; Yasuoka, Y.; Goto, T.; Kitamura, N.; Park, S.B.; Kishino, S.; Kimura, I.; Kasubuchi, M.; Takahashi, H.; Li, Y.; et al. alpha-Linolenic acid-derived metabolites from gut lactic acid bacteria induce differentiation of anti-inflammatory M2 macrophages through G protein-coupled receptor 40. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2018, 32, 304–318. [Google Scholar] [CrossRef] [Green Version]
- Sparks, S.M.; Chen, G.; Collins, J.L.; Danger, D.; Dock, S.T.; Jayawickreme, C.; Jenkinson, S.; Laudeman, C.; Leesnitzer, M.A.; Liang, X.; et al. Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). Bioorganic Med. Chem. Lett. 2014, 24, 3100–3103. [Google Scholar] [CrossRef]
- Wu, J.; Sun, P.; Zhang, X.; Liu, H.; Jiang, H.; Zhu, W.; Wang, H. Inhibition of GPR40 protects MIN6 beta cells from palmitate-induced ER stress and apoptosis. J. Cell. Biochem. 2012, 113, 1152–1158. [Google Scholar] [CrossRef]
- Wang, Y.; Xie, T.; Zhang, D.; Leung, P.S. GPR120 protects lipotoxicity-induced pancreatic beta-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation. Clin. Sci. 2019, 133, 101–116. [Google Scholar] [CrossRef]
- Dragano, N.R.V.; Solon, C.; Ramalho, A.F.; de Moura, R.F.; Razolli, D.S.; Christiansen, E.; Azevedo, C.; Ulven, T.; Velloso, L.A. Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation. J. Neuroinflamm. 2017, 14, 91. [Google Scholar] [CrossRef] [Green Version]
- Mo, Z.; Tang, C.; Li, H.; Lei, J.; Zhu, L.; Kou, L.; Luo, S.; Li, C.; Chen, W.; Zhang, L. Eicosapentaenoic acid prevents inflammation induced by acute cerebral infarction through inhibition of NLRP3 inflammasome activation. Life Sci. 2020, 242, 117133. [Google Scholar] [CrossRef]
- Low, Y.L.; Pan, Y.; Short, J.L.; Nicolazzo, J.A. Profiling the expression of fatty acid-binding proteins and fatty acid transporters in mouse microglia and assessing their role in docosahexaenoic acid-d5 uptake. Prostaglandins Leukot. Essent. Fat. Acids 2021, 171, 102303. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Cordes, K.R.; Farese, R.V., Jr.; Walther, T.C. Lipid droplets at a glance. J. Cell Sci. 2009, 122, 749–752. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Welte, M.A.; Gould, A.P. Lipid droplet functions beyond energy storage. Biochim. Et Biophys. Acta Mol. Cell Biol. Lipids 2017, 1862, 1260–1272. [Google Scholar] [CrossRef] [PubMed]
- Cheon, H.G.; Cho, Y.S. Protection of palmitic acid-mediated lipotoxicity by arachidonic acid via channeling of palmitic acid into triglycerides in C2C12. J. Biomed. Sci. 2014, 21, 13. [Google Scholar] [CrossRef] [Green Version]
- Almaguel, F.G.; Liu, J.W.; Pacheco, F.J.; Casiano, C.A.; De Leon, M. Activation and reversal of lipotoxicity in PC12 and rat cortical cells following exposure to palmitic acid. J. Neurosci. Res. 2009, 87, 1207–1218. [Google Scholar] [CrossRef] [Green Version]
- Li, P.; Li, L.; Zhang, C.; Cheng, X.; Zhang, Y.; Guo, Y.; Long, M.; Yang, S.; He, J. Palmitic Acid and beta-Hydroxybutyrate Induce Inflammatory Responses in Bovine Endometrial Cells by Activating Oxidative Stress-Mediated NF-kappaB Signaling. Molecules 2019, 24, 2421. [Google Scholar] [CrossRef] [Green Version]
- Yang, L.; Guan, G.; Lei, L.; Liu, J.; Cao, L.; Wang, X. Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis. Biosci. Rep. 2019, 39, BSR20190225. [Google Scholar] [CrossRef] [Green Version]
- Yuzefovych, L.; Wilson, G.; Rachek, L. Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: Role of oxidative stress. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E1096–E1105. [Google Scholar] [CrossRef] [Green Version]
- Suzuki, E.; Matsuda, T.; Kawamoto, T.; Takahashi, H.; Mieda, Y.; Matsuura, Y.; Takai, T.; Kanno, A.; Koyanagi-Kimura, M.; Asahara, S.I.; et al. Docosahexaenoic Acid Reduces Palmitic Acid-Induced Endoplasmic Reticulum Stress in Pancreatic Beta Cells. Kobe J. Med Sci. 2018, 64, E43–E55. [Google Scholar] [PubMed]
- Leyrolle, Q.; Laye, S.; Nadjar, A. Direct and indirect effects of lipids on microglia function. Neurosci. Lett. 2019, 708, 134348. [Google Scholar] [CrossRef] [PubMed]
- Lawson, L.J.; Perry, V.H.; Dri, P.; Gordon, S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 1990, 39, 151–170. [Google Scholar] [CrossRef]
- Streit, W.J.; Khoshbouei, H.; Bechmann, I. Dystrophic microglia in late-onset Alzheimer’s disease. Glia 2020, 68, 845–854. [Google Scholar] [CrossRef] [PubMed]
- Tracy, L.M.; Bergqvist, F.; Ivanova, E.V.; Jacobsen, K.T.; Iverfeldt, K. Exposure to the saturated free fatty acid palmitate alters BV-2 microglia inflammatory response. J. Mol. Neurosci. MN 2013, 51, 805–812. [Google Scholar] [CrossRef] [PubMed]
- Beaulieu, J.; Costa, G.; Renaud, J.; Moitie, A.; Glemet, H.; Sergi, D.; Martinoli, M.G. The Neuroinflammatory and Neurotoxic Potential of Palmitic Acid Is Mitigated by Oleic Acid in Microglial Cells and Microglial-Neuronal Co-cultures. Mol. Neurobiol. 2021, 58, 3000–3014. [Google Scholar] [CrossRef] [PubMed]
- Chausse, B.; Kakimoto, P.A.; Caldeira-da-Silva, C.C.; Chaves-Filho, A.B.; Yoshinaga, M.Y.; da Silva, R.P.; Miyamoto, S.; Kowaltowski, A.J. Distinct metabolic patterns during microglial remodeling by oleate and palmitate. Biosci. Rep. 2019, 39, BSR20190072. [Google Scholar] [CrossRef] [Green Version]
- Briscoe, C.P.; Tadayyon, M.; Andrews, J.L.; Benson, W.G.; Chambers, J.K.; Eilert, M.M.; Ellis, C.; Elshourbagy, N.A.; Goetz, A.S.; Minnick, D.T.; et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J. Biol. Chem. 2003, 278, 11303–11311. [Google Scholar] [CrossRef] [Green Version]
- Oh, D.Y.; Lagakos, W.S. The role of G-protein-coupled receptors in mediating the effect of fatty acids on inflammation and insulin sensitivity. Curr. Opin. Clin. Nutr. Metab. Care 2011, 14, 322–327. [Google Scholar] [CrossRef]
- Talukdar, S.; Olefsky, J.M.; Osborn, O. Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol. Sci. 2011, 32, 543–550. [Google Scholar] [CrossRef] [Green Version]
- Kuda, O.; Pietka, T.A.; Demianova, Z.; Kudova, E.; Cvacka, J.; Kopecky, J.; Abumrad, N.A. Sulfo-N-succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164: SSO also inhibits oxidized low density lipoprotein uptake by macrophages. J. Biol. Chem. 2013, 288, 15547–15555. [Google Scholar] [CrossRef] [Green Version]
- Quinlivan, V.H.; Wilson, M.H.; Ruzicka, J.; Farber, S.A. An HPLC-CAD/fluorescence lipidomics platform using fluorescent fatty acids as metabolic tracers. J. Lipid Res. 2017, 58, 1008–1020. [Google Scholar] [CrossRef] [Green Version]
- Malhi, H.; Gores, G.J. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin. Liver Dis. 2008, 28, 360–369. [Google Scholar] [CrossRef] [Green Version]
- Abdelmagid, S.A.; Clarke, S.E.; Nielsen, D.E.; Badawi, A.; El-Sohemy, A.; Mutch, D.M.; Ma, D.W. Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults. PLoS ONE 2015, 10, e0116195. [Google Scholar] [CrossRef] [Green Version]
- de Vries, J.E.; Vork, M.M.; Roemen, T.H.; de Jong, Y.F.; Cleutjens, J.P.; van der Vusse, G.J.; van Bilsen, M. Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J. Lipid Res. 1997, 38, 1384–1394. [Google Scholar] [CrossRef]
- Cnop, M.; Hannaert, J.C.; Hoorens, A.; Eizirik, D.L.; Pipeleers, D.G. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 2001, 50, 1771–1777. [Google Scholar] [CrossRef] [Green Version]
- Wei, Y.; Wang, D.; Topczewski, F.; Pagliassotti, M.J. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am. J. Physiol. Endocrinol. Metab. 2006, 291, E275–E281. [Google Scholar] [CrossRef]
- Cao, J.; Dai, D.L.; Yao, L.; Yu, H.H.; Ning, B.; Zhang, Q.; Chen, J.; Cheng, W.H.; Shen, W.; Yang, Z.X. Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol. Cell. Biochem. 2012, 364, 115–129. [Google Scholar] [CrossRef] [PubMed]
- Sieber, J.; Lindenmeyer, M.T.; Kampe, K.; Campbell, K.N.; Cohen, C.D.; Hopfer, H.; Mundel, P.; Jehle, A.W. Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids. Am. J. Physiol. Renal. Physiol. 2010, 299, F821–F829. [Google Scholar] [CrossRef] [Green Version]
- Mayer, C.M.; Belsham, D.D. Palmitate attenuates insulin signaling and induces endoplasmic reticulum stress and apoptosis in hypothalamic neurons: Rescue of resistance and apoptosis through adenosine 5’ monophosphate-activated protein kinase activation. Endocrinology 2010, 151, 576–585. [Google Scholar] [CrossRef] [PubMed]
- Zhou, H.; Urso, C.J.; Jadeja, V. Saturated Fatty Acids in Obesity-Associated Inflammation. J. Inflamm. Res. 2020, 13, 1–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Labat-Moleur, F.; Guillermet, C.; Lorimier, P.; Robert, C.; Lantuejoul, S.; Brambilla, E.; Negoescu, A. TUNEL apoptotic cell detection in tissue sections: Critical evaluation and improvement. J. Histochem. Cytochem. Off. J. Histochem. Soc. 1998, 46, 327–334. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Crowley, L.C.; Marfell, B.J.; Scott, A.P.; Waterhouse, N.J. Quantitation of Apoptosis and Necrosis by Annexin V Binding, Propidium Iodide Uptake, and Flow Cytometry. Cold Spring Harb. Protoc. 2016, 2016. [Google Scholar] [CrossRef] [PubMed]
- Hara, T.; Hirasawa, A.; Ichimura, A.; Kimura, I.; Tsujimoto, G. Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J. Pharm. Sci. 2011, 100, 3594–3601. [Google Scholar] [CrossRef] [PubMed]
- Kristinsson, H.; Smith, D.M.; Bergsten, P.; Sargsyan, E. FFAR1 is involved in both the acute and chronic effects of palmitate on insulin secretion. Endocrinology 2013, 154, 4078–4088. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lan, H.; Hoos, L.M.; Liu, L.; Tetzloff, G.; Hu, W.; Abbondanzo, S.J.; Vassileva, G.; Gustafson, E.L.; Hedrick, J.A.; Davis, H.R. Lack of FFAR1/GPR40 does not protect mice from high-fat diet-induced metabolic disease. Diabetes 2008, 57, 2999–3006. [Google Scholar] [CrossRef] [Green Version]
- Panse, M.; Gerst, F.; Kaiser, G.; Teutsch, C.A.; Dolker, R.; Wagner, R.; Haring, H.U.; Ullrich, S. Activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) by free fatty acid receptor 1 (FFAR1/GPR40) protects from palmitate-induced beta cell death, but plays no role in insulin secretion. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2015, 35, 1537–1545. [Google Scholar] [CrossRef] [PubMed]
- Christiansen, E.; Watterson, K.R.; Stocker, C.J.; Sokol, E.; Jenkins, L.; Simon, K.; Grundmann, M.; Petersen, R.K.; Wargent, E.T.; Hudson, B.D.; et al. Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br. J. Nutr. 2015, 113, 1677–1688. [Google Scholar] [CrossRef] [Green Version]
- Cosgrove, J.P.; Church, D.F.; Pryor, W.A. The kinetics of the autoxidation of polyunsaturated fatty acids. Lipids 1987, 22, 299–304. [Google Scholar] [CrossRef]
- Iuchi, K.; Ema, M.; Suzuki, M.; Yokoyama, C.; Hisatomi, H. Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells. Mol. Med. Rep. 2019, 19, 2767–2773. [Google Scholar] [CrossRef] [Green Version]
- Elmazoglu, Z.; Prnova, M.S.; Stefek, M.; Ceylan, A.F.; Aschner, M.; Rangel-Lopez, E.; Santamaria, A.; Karasu, C. Protective Effects of Novel Substituted Triazinoindole Inhibitors of Aldose Reductase and Epalrestat in Neuron-like PC12 Cells and BV2 Rodent Microglial Cells Exposed to Toxic Models of Oxidative Stress: Comparison with the Pyridoindole Antioxidant Stobadine. Neurotox. Res. 2021, 39, 588–597. [Google Scholar] [CrossRef]
- Jarc, E.; Petan, T. Lipid Droplets and the Management of Cellular Stress. Yale J. Biol. Med. 2019, 92, 435–452. [Google Scholar]
- Plotz, T.; Hartmann, M.; Lenzen, S.; Elsner, M. The role of lipid droplet formation in the protection of unsaturated fatty acids against palmitic acid induced lipotoxicity to rat insulin-producing cells. Nutr. Metab. 2016, 13, 16. [Google Scholar] [CrossRef] [Green Version]
- Olzmann, J.A.; Carvalho, P. Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol. 2019, 20, 137–155. [Google Scholar] [CrossRef] [PubMed]
- Park, E.J.; Lee, A.Y.; Park, S.; Kim, J.H.; Cho, M.H. Multiple pathways are involved in palmitic acid-induced toxicity. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc. 2014, 67, 26–34. [Google Scholar] [CrossRef] [PubMed]
- Tumova, J.; Malisova, L.; Andel, M.; Trnka, J. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARdelta Activation. Lipids 2015, 50, 955–964. [Google Scholar] [CrossRef]
- Gehrmann, W.; Wurdemann, W.; Plotz, T.; Jorns, A.; Lenzen, S.; Elsner, M. Antagonism Between Saturated and Unsaturated Fatty Acids in ROS Mediated Lipotoxicity in Rat Insulin-Producing Cells. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2015, 36, 852–865. [Google Scholar] [CrossRef]
- Zeng, X.; Zhu, M.; Liu, X.; Chen, X.; Yuan, Y.; Li, L.; Liu, J.; Lu, Y.; Cheng, J.; Chen, Y. Oleic acid ameliorates palmitic acid induced hepatocellular lipotoxicity by inhibition of ER stress and pyroptosis. Nutr. Metab. 2020, 17, 11. [Google Scholar] [CrossRef] [Green Version]
- Egnatchik, R.A.; Leamy, A.K.; Noguchi, Y.; Shiota, M.; Young, J.D. Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes. Metab. Clin. Exp. 2014, 63, 283–295. [Google Scholar] [CrossRef] [Green Version]
- Zou, L.; Li, X.; Wu, N.; Jia, P.; Liu, C.; Jia, D. Palmitate induces myocardial lipotoxic injury via the endoplasmic reticulum stressmediated apoptosis pathway. Mol. Med. Rep. 2017, 16, 6934–6939. [Google Scholar] [CrossRef]
- Osorio, D.; Pinzon, A.; Martin-Jimenez, C.; Barreto, G.E.; Gonzalez, J. Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach. Front. Neurosci. 2019, 13, 1410. [Google Scholar] [CrossRef] [Green Version]
- Dye, L.; Boyle, N.B.; Champ, C.; Lawton, C. The relationship between obesity and cognitive health and decline. Proc. Nutr. Soc. 2017, 76, 443–454. [Google Scholar] [CrossRef] [Green Version]
- Ivanova, N.; Liu, Q.; Agca, C.; Agca, Y.; Noble, E.G.; Whitehead, S.N.; Cechetto, D.F. White matter inflammation and cognitive function in a co-morbid metabolic syndrome and prodromal Alzheimer’s disease rat model. J. Neuroinflamm. 2020, 17, 29. [Google Scholar] [CrossRef] [Green Version]
- Lee, J.E.; Shin, D.W.; Han, K.; Kim, D.; Yoo, J.E.; Lee, J.; Kim, S.; Son, K.Y.; Cho, B.; Kim, M.J. Changes in Metabolic Syndrome Status and Risk of Dementia. J. Clin. Med. 2020, 9, 122. [Google Scholar] [CrossRef] [Green Version]
- Urso, C.J.Z.H. Differential Effects of Unsaturated Fatty Acids and Saturated Fatty Acids in Lipotoxicity and Neutral Lipid Accumulation in Neuro-2a Cells. Biomed. J. Sci. Tech. Res. 2021, 37, 29516–29524. [Google Scholar] [CrossRef]
- Richieri, G.V.; Kleinfeld, A.M. Unbound free fatty acid levels in human serum. J. Lipid Res. 1995, 36, 229–240. [Google Scholar] [CrossRef]
- Le Rouzic, V.; Corona, J.; Zhou, H. Postnatal development of hepatic innate immune response. Inflammation 2011, 34, 576–584. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ortega, A.; Jadeja, V.; Zhou, H. Postnatal development of lipopolysaccharide-induced inflammatory response in the brain. Inflamm. Res. 2011, 60, 175–185. [Google Scholar] [CrossRef] [PubMed]
- Barabas, P.; Liu, A.; Xing, W.; Chen, C.K.; Tong, Z.; Watt, C.B.; Jones, B.W.; Bernstein, P.S.; Krizaj, D. Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degeneration. Proc. Natl. Acad. Sci. USA 2013, 110, 5181–5186. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 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
Urso, C.J.; Zhou, H. Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids. Int. J. Mol. Sci. 2021, 22, 9093. https://doi.org/10.3390/ijms22169093
Urso CJ, Zhou H. Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids. International Journal of Molecular Sciences. 2021; 22(16):9093. https://doi.org/10.3390/ijms22169093
Chicago/Turabian StyleUrso, C.J., and Heping Zhou. 2021. "Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids" International Journal of Molecular Sciences 22, no. 16: 9093. https://doi.org/10.3390/ijms22169093