Effect of transient receptor potential vanilloid 4 agonist on lipid metabolism in adipocytes based on metabolomics_West China Medical Journal

Authors：

HUANG Jialu , LUO Ling , JIN Zhimei , YANG Zihua , CAO Rudai , WU Shufa ,  DING Yuanlin ,  YU Haibing

Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan, Guangdong 523808, P. R. China;

Corresponding author：

DING Yuanlin, Email: gdmusbd@gdmu.edu.cn; YU Haibing, Email: hby616688@gdmu.edu.cn

Keywords：

Transient receptor potential vanilloid 4; lipid metabolism; agonist; metabolomics; biomarker

DOI：

10.7507/1002-0179.202302092

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the metabolic changes during the differentiation of 3T3-L1 adipocytes caused by the treatment of the transient receptor potential vanilloid 4 (TRPV4)-specific agonist GSK1016790A basing on ultra-performance liquid chromatography-mass spectrometry technology. Methods Mouse 3T3-L1 cells were treated with GSK1016790A at different concentrations (0.1, 1, and 10 μmol/L), and the effect of drugs on cell proliferation was detected by cell counting kit-8 method. A mature adipocyte model was constructed, and GSK1016790A was used to activate TRPV4 channel protein activity and verify the expression levels of TRPV4 and triglycerides. Cell metabolites were collected for metabolomic studies, differential metabolites were screened between groups, and related metabolic pathways were analyzed. Results After GSK1016790A intervened in mature adipocytes, the expression levels of TRPV4 mRNA and triglycerides in cells were significantly upregulated (P<0.05). Metabolomics detection found that GSK1016790A screened a total of 45 differential metabolites such as 2-amino-1,3,4-octadecanetriol, linoleic acid, sphingosine, sphinganine, sn-glycerol-3-phosphate and uridine, mainly involving 13 possible metabolic pathways such as sphingolipid metabolism and biosynthesis of unsaturated fatty acids. Conclusion GSK1016790A may promote adipogenesis in adipocytes by activating TRPV4 channel protein activity, and at the same time participate in regulating metabolic pathways such as the biosynthesis of unsaturated fatty acids pathway and sphingolipid metabolism pathway, affecting lipid metabolism in adipocytes.

Citation： HUANG Jialu, LUO Ling, JIN Zhimei, YANG Zihua, CAO Rudai, WU Shufa, DING Yuanlin, YU Haibing. Effect of transient receptor potential vanilloid 4 agonist on lipid metabolism in adipocytes based on metabolomics. West China Medical Journal, 2023, 38(9): 1323-1332. doi: 10.7507/1002-0179.202302092 Copy

1.	Bleich S, Cutler D, Murray C, et al. Why is the developed world obese?. Annu Rev Public Health, 2008, 29: 273-295.
2.	Kannel WB, Cupples LA, Ramaswami R, et al. Regional obesity and risk of cardiovascular disease; the Framingham Study. J Clin Epidemiol, 1991, 44(2): 183-190.
3.	Field AE, Coakley EH, Must A, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med, 2001, 161(13): 1581-1586.
4.	Uchida K, Sun W, Yamazaki J, et al. Role of thermo-sensitive transient receptor potential channels in brown adipose tissue. Biol Pharm Bull, 2018, 41(8): 1135-1144.
5.	Xue B, Greenberg AG, Kraemer FB, et al. Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes. FASEB J, 2001, 15(13): 2527-2529.
6.	Liedtke W, Choe Y, Martí-Renom MA, et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 2000, 103(3): 525-535.
7.	Ahern GP. Transient receptor potential channels and energy homeostasis. Trends Endocrinol Metab, 2013, 24(11): 554-560.
8.	Ye L, Kleiner S, Wu J, et al. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell, 2012, 151(1): 96-110.
9.	Akopian A. Role of TRP ion channels in physiology and pathology. Semin Immunopathol, 2016, 38(3): 275-276.
10.	Grace MS, Bonvini SJ, Belvisi MG, et al. Modulation of the TRPV4 ion channel as a therapeutic target for disease. Pharmacol Ther, 2017, 177: 9-22.
11.	Thorneloe KS, Sulpizio AC, Lin Z, et al. N-((1S)-1-[4-((2S)-2-[(2, 4-dichlorophenyl)sulfonyl]amino-3-hydroxypropanoyl)-1-piperazinyl]carbonyl-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther, 2008, 326(2): 432-442.
12.	Lee HC, Yokomizo T. Applications of mass spectrometry-based targeted and non-targeted lipidomics. Biochem Biophys Res Commun, 2018, 504(3): 576-581.
13.	Steffens DC, Jiang W, Krishnan KR, et al. Metabolomic differences in heart failure patients with and without major depression. J Geriatr Psychiatry Neurol, 2010, 23(2): 138-146.
14.	Sassa T, Suto S, Okayasu Y, et al. A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells. Biochim Biophys Acta, 2012, 1821(7): 1031-1037.
15.	Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol, 2008, 9(2): 139-150.
16.	Merrill AH Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem, 2002, 277(29): 25843-25846.
17.	Samad F, Hester KD, Yang G, et al. Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk. Diabetes, 2006, 55(9): 2579-2587.
18.	Palhinha L, Liechocki S, Hottz ED, et al. Leptin induces proadipogenic and proinflammatory signaling in adipocytes. Front Endocrinol (Lausanne), 2019, 10: 841.
19.	Naughton SS, Mathai ML, Hryciw DH, et al. Linoleic acid and the pathogenesis of obesity. Prostaglandins Other Lipid Mediat, 2016, 125: 90-99.
20.	Shao X, Wang M, Wei X, et al. Peroxisome proliferator-activated receptor-γ: master regulator of adipogenesis and obesity. Curr Stem Cell Res Ther, 2016, 11(3): 282-289.
21.	Vidal-Puig AJ, Considine RV, Jimenez-Liñan M, et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest, 1997, 99(10): 2416-2422.
22.	陈永熙, 王伟铭, 周同, 等. PPAR-γ 作用及其相关信号转导途径. 细胞生物学杂志, 2006, 28(3): 382-386.

1. Bleich S, Cutler D, Murray C, et al. Why is the developed world obese?. Annu Rev Public Health, 2008, 29: 273-295.
2. Kannel WB, Cupples LA, Ramaswami R, et al. Regional obesity and risk of cardiovascular disease; the Framingham Study. J Clin Epidemiol, 1991, 44(2): 183-190.
3. Field AE, Coakley EH, Must A, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med, 2001, 161(13): 1581-1586.
4. Uchida K, Sun W, Yamazaki J, et al. Role of thermo-sensitive transient receptor potential channels in brown adipose tissue. Biol Pharm Bull, 2018, 41(8): 1135-1144.
5. Xue B, Greenberg AG, Kraemer FB, et al. Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes. FASEB J, 2001, 15(13): 2527-2529.
6. Liedtke W, Choe Y, Martí-Renom MA, et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell, 2000, 103(3): 525-535.
7. Ahern GP. Transient receptor potential channels and energy homeostasis. Trends Endocrinol Metab, 2013, 24(11): 554-560.
8. Ye L, Kleiner S, Wu J, et al. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell, 2012, 151(1): 96-110.
9. Akopian A. Role of TRP ion channels in physiology and pathology. Semin Immunopathol, 2016, 38(3): 275-276.
10. Grace MS, Bonvini SJ, Belvisi MG, et al. Modulation of the TRPV4 ion channel as a therapeutic target for disease. Pharmacol Ther, 2017, 177: 9-22.
11. Thorneloe KS, Sulpizio AC, Lin Z, et al. N-((1S)-1-[4-((2S)-2-[(2, 4-dichlorophenyl)sulfonyl]amino-3-hydroxypropanoyl)-1-piperazinyl]carbonyl-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther, 2008, 326(2): 432-442.
12. Lee HC, Yokomizo T. Applications of mass spectrometry-based targeted and non-targeted lipidomics. Biochem Biophys Res Commun, 2018, 504(3): 576-581.
13. Steffens DC, Jiang W, Krishnan KR, et al. Metabolomic differences in heart failure patients with and without major depression. J Geriatr Psychiatry Neurol, 2010, 23(2): 138-146.
14. Sassa T, Suto S, Okayasu Y, et al. A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells. Biochim Biophys Acta, 2012, 1821(7): 1031-1037.
15. Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol, 2008, 9(2): 139-150.
16. Merrill AH Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem, 2002, 277(29): 25843-25846.
17. Samad F, Hester KD, Yang G, et al. Altered adipose and plasma sphingolipid metabolism in obesity: a potential mechanism for cardiovascular and metabolic risk. Diabetes, 2006, 55(9): 2579-2587.
18. Palhinha L, Liechocki S, Hottz ED, et al. Leptin induces proadipogenic and proinflammatory signaling in adipocytes. Front Endocrinol (Lausanne), 2019, 10: 841.
19. Naughton SS, Mathai ML, Hryciw DH, et al. Linoleic acid and the pathogenesis of obesity. Prostaglandins Other Lipid Mediat, 2016, 125: 90-99.
20. Shao X, Wang M, Wei X, et al. Peroxisome proliferator-activated receptor-γ: master regulator of adipogenesis and obesity. Curr Stem Cell Res Ther, 2016, 11(3): 282-289.
21. Vidal-Puig AJ, Considine RV, Jimenez-Liñan M, et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest, 1997, 99(10): 2416-2422.
22. 陈永熙, 王伟铭, 周同, 等. PPAR-γ 作用及其相关信号转导途径. 细胞生物学杂志, 2006, 28(3): 382-386.

West China Medical Journal

Effect of transient receptor potential vanilloid 4 agonist on lipid metabolism in adipocytes based on metabolomics

Abstract Full text Figures/Tables Video References Cited by

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