Flazin as a Lipid Droplet Regulator against Lipid Disorders
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Culture and Treatment
2.3. Cellular Lipid Extraction
2.4. LC/MS and MS/MS Analysis
2.5. Oil Red O Staining
2.6. LD Analysis by NanoESI-MS
2.7. Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR)
2.8. Statistical Analysis
3. Results
3.1. Flazin Improved Cellular Lipid Content and Profile
3.1.1. Cell Viability
3.1.2. TG and FFA Content
3.1.3. TG Profile and FFA Characteristics
3.2. Flazin Alleviated LD Accretion
3.3. Flazin Reduced TG Level in LDs
3.4. Flazin Regulate Surface Properties of LDs
3.5. Flazin Regulated mRNA Expression of Lipogenic and Lipolytic Genes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Whaley-Connell, A.; Sowers, J.R. Obesity and kidney disease: From population to basic science and the search for new therapeutic targets. Kidney Int. 2017, 92, 313–323. [Google Scholar] [CrossRef] [PubMed]
- Moghadasian, M.H.; Kaur, R.; Kostal, K.; Joshi, A.A.; Molaei, M.; Le, K.; Fischer, G.; Bonomini, F.; Favero, G.; Rezzani, R.; et al. Anti-Atherosclerotic Properties of Wild Rice in Low-Density Lipoprotein Receptor Knockout Mice: The Gut Microbiome, Cytokines, and Metabolomics Study. Nutrients 2019, 11, 2894. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kotlyarov, S.; Bulgakov, A. Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease. Cells 2021, 10, 2978. [Google Scholar] [CrossRef]
- Hou, C.; Zhang, W.; Li, J.; Du, L.; Lv, O.; Zhao, S.; Li, J. Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders. Mol. Nutr. Food Res. 2019, 63, 1800773. [Google Scholar] [CrossRef]
- Heindel, J.J.; Blumberg, B.; Cave, M.; Machtinger, R.; Mantovani, A.; Mendez, M.A.; Nadal, A.; Palanza, P.; Panzica, G.; Sargis, R.; et al. Metabolism disrupting chemicals and metabolic disorders. Reprod. Toxicol. 2017, 68, 3–33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guebre-Egziabher, F.; Alix, P.M.; Koppe, L.; Pelletier, C.C.; Kalbacher, E.; Fouque, D.; Soulage, C.O. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function. Biochimie 2013, 95, 1971–1979. [Google Scholar] [CrossRef]
- Thongnak, L.; Pongchaidecha, A.; Lungkaphin, A. Renal Lipid Metabolism and Lipotoxicity in Diabetes. Am. J. Med. Sci. 2020, 359, 84–99. [Google Scholar] [CrossRef]
- Han, Y.; Xiong, S.; Zhao, H.; Yang, S.; Yang, M.; Zhu, X.; Jiang, N.; Xiong, X.; Gao, P.; Wei, L.; et al. Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy. Cell Death Dis. 2021, 12, 1031. [Google Scholar] [CrossRef]
- Santana, L.F.; Inada, A.C.; Espirito Santo, B.L.S.d.; Filiú, W.F.O.; Pott, A.; Alves, F.M.; Guimarães, R.d.C.A.; Freitas, K.d.C.; Hiane, P.A. Nutraceutical Potential of Carica papaya in Metabolic Syndrome. Nutrients 2019, 11, 1608. [Google Scholar] [CrossRef] [Green Version]
- Siddiqui, R.A.; Moghadasian, M.H. Nutraceuticals and Nutrition Supplements: Challenges and Opportunities. Nutrients 2020, 12, 1593. [Google Scholar] [CrossRef]
- Nakatsuka, S.; Feng, B.; Goto, T.; Kihara, K. Structures of flazin and YS, highly fluorescent compounds isolated from japanese soy sauce. Tetrahedron Lett. 1986, 27, 3399–3402. [Google Scholar] [CrossRef]
- Seong, S.H.; Jung, H.A.; Choi, J.S. Discovery of Flazin, an Alkaloid Isolated from Cherry Tomato Juice, As a Novel Non-Enzymatic Protein Glycation Inhibitor via in Vitro and in Silico Studies. J. Agric. Food Chem. 2021, 69, 3647–3657. [Google Scholar] [CrossRef] [PubMed]
- Mäkilä, L.; Laaksonen, O.; Alanne, A.-L.; Kortesniemi, M.; Kallio, H.; Yang, B. Stability of Hydroxycinnamic Acid Derivatives, Flavonol Glycosides, and Anthocyanins in Black Currant Juice. J. Agric. Food Chem. 2016, 64, 4584–4598. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.-Q.; Wang, Y.-M.; Yang, Y.-L.; Zeng, Y.; Wang, Q.-L.; Shao, Y.; Mei, L.-J.; Shi, Y.-P.; Tao, Y.-D. Isolation and identification of antioxidant and α-glucosidase inhibitory compounds from fruit juice of Nitraria tangutorum. Food Chem. 2017, 227, 93–101. [Google Scholar] [CrossRef] [PubMed]
- Tang, J.-G.; Wang, Y.-H.; Wang, R.-R.; Dong, Z.-J.; Yang, L.-M.; Zheng, Y.-T.; Liu, J.-K. Synthesis of Analogues of Flazin, in Particular, Flazinamide, as Promising Anti-HIV Agents. Chem. Biodivers. 2008, 5, 447–460. [Google Scholar] [CrossRef] [PubMed]
- Fuda, H.; Miyanaga, S.; Furukawa, T.; Umetsu, S.; Joko, S.; Roan, Y.; Suzuki, H.; Hui, S.-P.; Watanabe, M.; Chiba, H. Flazin as a Promising Nrf2 Pathway Activator. J. Agric. Food Chem. 2019, 67, 12844–12853. [Google Scholar] [CrossRef]
- Kong, Y.; Wang, L.-H.; Liu, L.; Zheng, L.-H.; Bao, Y.-L.; Liu, X.-X.; Wang, S.-Y.; Song, Z.-B. Immunomodulatory effects of flazin from Crassostrea sikamea on splenic lymphocytes of Sprague-Dawley rats. Chin. J. Nat. Med. 2021, 19, 836–843. [Google Scholar] [CrossRef]
- Baylin, A.; Kabagambe, E.K.; Siles, X.; Campos, H. Adipose tissue biomarkers of fatty acid intake. Am. J. Clin. Nutr. 2002, 76, 750–757. [Google Scholar] [CrossRef] [Green Version]
- Zheng, B.; Trieu, T.H.; Meng, T.-Z.; Lu, X.; Dong, J.; Zhang, Q.; Shi, X.-X. Cu-catalyzed mild and efficient oxidation of THβCs using air: Application in practical total syntheses of perlolyrine and flazin. RSC Adv. 2018, 8, 6834–6839. [Google Scholar] [CrossRef] [Green Version]
- Wang, P.; Kong, F.; Wei, J.; Wang, Y.; Wang, W.; Hong, K.; Zhu, W. Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111. Mar. Drugs 2014, 12, 477–490. [Google Scholar] [CrossRef] [Green Version]
- Ulloth, J.E.; Casiano, C.A.; De Leon, M. Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells. J. Neurochem. 2003, 84, 655–668. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matyash, V.; Liebisch, G.; Kurzchalia, T.V.; Shevchenko, A.; Schwudke, D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J. Lipid Res. 2008, 49, 1137–1146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, Y.; Chen, Z.; Fuda, H.; Tsukui, T.; Wu, X.; Shen, N.; Saito, N.; Chiba, H.; Hui, S.P. Oxidative stress linked organ lipid hydroperoxidation and dysregulation in mouse model of nonalcoholic steatohepatitis: Revealed by lipidomic profiling of liver and kidney. Antioxidants 2021, 10, 602. [Google Scholar] [CrossRef] [PubMed]
- Schneider, C.A.; Rasband, W.S.; Eliceiri, K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 2012, 9, 671–675. [Google Scholar] [CrossRef]
- Zhao, Y.; Chen, Z.; Wu, Y.; Tsukui, T.; Ma, X.; Zhang, X.; Chiba, H.; Hui, S.-P. Separating and Profiling Phosphatidylcholines and Triglycerides from Single Cellular Lipid Droplet by In-Tip Solvent Microextraction Mass Spectrometry. Anal. Chem. 2019, 91, 4466–4471. [Google Scholar] [CrossRef]
- Warensjö, E.; Rosell, M.; Hellenius, M.-L.; Vessby, B.; De Faire, U.; Risérus, U. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: Links to obesity and insulin resistance. Lipids Health Dis. 2009, 8, 37. [Google Scholar] [CrossRef] [Green Version]
- Listenberger, L.; Townsend, E.; Rickertsen, C.; Hains, A.; Brown, E.; Inwards, E.; Stoeckman, A.; Matis, M.; Sampathkumar, R.; Osna, N.; et al. Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis. Cells 2018, 7, 230. [Google Scholar] [CrossRef] [Green Version]
- Haemmerle, G.; Lass, A.; Zimmermann, R.; Gorkiewicz, G.; Meyer, C.; Rozman, J.; Heldmaier, G.; Maier, R.; Theussl, C.; Eder, S.; et al. Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase. Science 2006, 312, 734–737. [Google Scholar] [CrossRef]
- Zhang, H.-J.; Gao, X.; Guo, X.-F.; Li, K.-L.; Li, S.; Sinclair, A.J.; Li, D. Effects of dietary eicosapentaenoic acid and docosahexaenoic acid supplementation on metabolic syndrome: A systematic review and meta-analysis of data from 33 randomized controlled trials. Clin. Nutr. 2021, 40, 4538–4550. [Google Scholar] [CrossRef]
- Testa, R.; Bonfigli, A.; Genovese, S.; De Nigris, V.; Ceriello, A. The Possible Role of Flavonoids in the Prevention of Diabetic Complications. Nutrients 2016, 8, 310. [Google Scholar] [CrossRef] [Green Version]
- Den Hartogh, D.J.; Gabriel, A.; Tsiani, E. Antidiabetic Properties of Curcumin II: Evidence from In Vivo Studies. Nutrients 2019, 12, 58. [Google Scholar] [CrossRef] [PubMed] [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]
- Paton, C.M.; Ntambi, J.M. Biochemical and physiological function of stearoyl-CoA desaturase. Am. J. Physiol.-Endocrinol. Metab. 2009, 297, 28–37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, H.; Galea, A.; Sytnyk, V.; Crossley, M. Controlling the size of lipid droplets: Lipid and protein factors. Curr. Opin. Cell Biol. 2012, 24, 509–516. [Google Scholar] [CrossRef]
- Guo, Y.; Walther, T.C.; Rao, M.; Stuurman, N.; Goshima, G.; Terayama, K.; Wong, J.S.; Vale, R.D.; Walter, P.; Farese, R.V. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature 2008, 453, 657–661. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krahmer, N.; Guo, Y.; Wilfling, F.; Hilger, M.; Lingrell, S.; Heger, K.; Newman, H.W.; Schmidt-Supprian, M.; Vance, D.E.; Mann, M.; et al. Phosphatidylcholine Synthesis for Lipid Droplet Expansion Is Mediated by Localized Activation of CTP:Phosphocholine Cytidylyltransferase. Cell Metab. 2011, 14, 504–515. [Google Scholar] [CrossRef] [Green Version]
- Bacle, A.; Gautier, R.; Jackson, C.L.; Fuchs, P.F.J.; Vanni, S. Interdigitation between Triglycerides and Lipids Modulates Surface Properties of Lipid Droplets. Biophys. J. 2017, 112, 1417–1430. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.; Agellon, L.B.; Allen, T.M.; Umeda, M.; Jewell, L.; Mason, A.; Vance, D.E. The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab. 2006, 3, 321–331. [Google Scholar] [CrossRef] [Green Version]
- Missaglia, S.; Coleman, R.; Mordente, A.; Tavian, D. Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function. Cells 2019, 8, 187. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 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
Wu, X.; Chen, Z.; Wu, Y.; Chen, Y.; Jia, J.; Shen, N.; Chiba, H.; Hui, S.-P. Flazin as a Lipid Droplet Regulator against Lipid Disorders. Nutrients 2022, 14, 1501. https://doi.org/10.3390/nu14071501
Wu X, Chen Z, Wu Y, Chen Y, Jia J, Shen N, Chiba H, Hui S-P. Flazin as a Lipid Droplet Regulator against Lipid Disorders. Nutrients. 2022; 14(7):1501. https://doi.org/10.3390/nu14071501
Chicago/Turabian StyleWu, Xunzhi, Zhen Chen, Yue Wu, Yifan Chen, Jiaping Jia, Nianqiu Shen, Hitoshi Chiba, and Shu-Ping Hui. 2022. "Flazin as a Lipid Droplet Regulator against Lipid Disorders" Nutrients 14, no. 7: 1501. https://doi.org/10.3390/nu14071501