TRPV4 deficiency increases skeletal muscle metabolic capacity and resistance against diet-induced obesity
- PMID: 22207724
- DOI: 10.1152/japplphysiol.01070.2011
TRPV4 deficiency increases skeletal muscle metabolic capacity and resistance against diet-induced obesity
Abstract
Transient receptor potential channel V4 (TRPV4) functions as a nonselective cation channel in various cells and plays physiological roles in osmotic and thermal sensation. However, the function of TRPV4 in energy metabolism is unknown. Here, we report that TRPV4 deficiency results in increased muscle oxidative capacity and resistance to diet-induced obesity in mice. Although no difference in body weight was observed between wild-type and Trpv4(-/-) mice when fed a standard chow diet, obesity phenotypes induced by a high-fat diet were significantly improved in Trpv4(-/-) mice, without any change in food intake. Quantitative analysis of mRNA revealed the constitutive upregulation of many genes, including those for transcription factors such as peroxisome proliferator-activated receptor α and for metabolic enzymes such as phosphoenolpyruvate carboxykinase. These upregulated genes were especially prominent in oxidative skeletal muscle, in which the activity of Ca(2+)-dependent phosphatase calcineurin was elevated, suggesting that other Ca(2+) channels function in the skeletal muscle of Trpv4(-/-) mice. Indeed, gene expressions for TRPC3 and TRPC6 increased in the muscles of Trpv4(-/-) mice compared with those of wild-type mice. The number of oxidative type I fiber also increased in the mutant muscles following myogenin gene induction. These results strongly suggested that inactivation of Trpv4 induces compensatory increases in TRPC3 and TRPC6 production, and elevation of calcineurin activity, affecting energy metabolism through increased expression of genes involved in fuel oxidation in skeletal muscle and thereby contributing to increased energy expenditure and protection from diet-induced obesity in mice.
Similar articles
-
Different contribution of muscle and liver lipid metabolism to endurance capacity and obesity susceptibility of mice.J Appl Physiol (1985). 2009 Mar;106(3):871-9. doi: 10.1152/japplphysiol.90804.2008. Epub 2009 Jan 8. J Appl Physiol (1985). 2009. PMID: 19131482
-
Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle.Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E831-40. doi: 10.1152/ajpendo.00339.2011. Epub 2012 Jan 24. Am J Physiol Endocrinol Metab. 2012. PMID: 22275756
-
Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains.BMC Genomics. 2006 Jun 20;7:159. doi: 10.1186/1471-2164-7-159. BMC Genomics. 2006. PMID: 16787531 Free PMC article.
-
The TRPV4 channel.Handb Exp Pharmacol. 2014;222:293-319. doi: 10.1007/978-3-642-54215-2_12. Handb Exp Pharmacol. 2014. PMID: 24756711 Review.
-
[Pathophysiological roles of transient receptor potential channels in glial cells].Yakugaku Zasshi. 2010 Mar;130(3):281-7. doi: 10.1248/yakushi.130.281. Yakugaku Zasshi. 2010. PMID: 20190511 Review. Japanese.
Cited by
-
The nonselective cation channel TRPV4 inhibits angiotensin II receptors.J Biol Chem. 2020 Jul 17;295(29):9986-9997. doi: 10.1074/jbc.RA120.014325. Epub 2020 Jun 3. J Biol Chem. 2020. PMID: 32493776 Free PMC article.
-
Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes-related complications.J Diabetes Investig. 2020 Jul;11(4):757-769. doi: 10.1111/jdi.13244. Epub 2020 Apr 16. J Diabetes Investig. 2020. PMID: 32129549 Free PMC article. Review.
-
Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets.Front Pharmacol. 2016 Mar 30;7:58. doi: 10.3389/fphar.2016.00058. eCollection 2016. Front Pharmacol. 2016. PMID: 27065858 Free PMC article. Review.
-
Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid requires protein kinase A-mediated phosphorylation.J Biol Chem. 2018 Apr 6;293(14):5307-5322. doi: 10.1074/jbc.M117.811075. Epub 2018 Feb 8. J Biol Chem. 2018. PMID: 29462784 Free PMC article.
-
Involvement of TRP Channels in Adipocyte Thermogenesis: An Update.Front Cell Dev Biol. 2021 Jun 24;9:686173. doi: 10.3389/fcell.2021.686173. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34249940 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Miscellaneous