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Troglitazone activates TRPV1 and causes deacetylation of PPAR? in 3T3-L1 cells.

ABSTRACT: Published research suggests that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) enhances the expression and deacetylation of peroxisome proliferator-activated receptor gamma (PPAR?) to cause browning of white adipose tissue. Here, we show that TRPV1 activation by capsaicin significantly prevents high fat diet-induced obesity in mice. This is associated with an increase in the expression and deacetylation of PPAR? in the epididymal fat of these mice. Consistent with the TRPV1 activation in vivo, overexpression of TRPV1 enhanced the PPAR? and other thermogenic genes in cultured 3T3-L1 preadipocytes. To determine the interaction between TRPV1 and PPAR? signaling, we analyzed the effect of Troglitazone (Trog; a thiazolidinedione derivative and an agonist of PAAR?) treatment on cultured 3T3-L1 cells. Trog enhanced the expression of TRPV1, PPAR? and thermogenic proteins in undifferentiated 3T3-L1 cells but not in differentiated cells. Acute application of Trog stimulated a robust Ca2+ influx into 3T3-L1 cells and TRPV1 inhibition by capsazepine prevented this. More interestingly, Trog or capsaicin treatment caused the deacetylation of PPAR? in 3T3-L1 cells and inhibition of TRPV1 or Sirtuin 1 - prevented this. Our data suggest a novel effect of Trog to induce PPAR? deacetylation by activating TRPV1. This research has a significant implication on the role of TRPV1 and PPAR? signaling in the browning of white adipose tissue.

SUBMITTER: Krishnan V

PROVIDER: S-EPMC6364553 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Troglitazone activates TRPV1 and causes deacetylation of PPARγ in 3T3-L1 cells.

Krishnan Vivek V Baskaran Padmamalini P Thyagarajan Baskaran B

Biochimica et biophysica acta. Molecular basis of disease 20181126 2

Published research suggests that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) enhances the expression and deacetylation of peroxisome proliferator-activated receptor gamma (PPARγ) to cause browning of white adipose tissue. Here, we show that TRPV1 activation by capsaicin significantly prevents high fat diet-induced obesity in mice. This is associated with an increase in the expression and deacetylation of PPARγ in the epididymal fat of these mice. Consistent with the ...[more]

PMID: 30496795

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Project description:Gegen Qinlian Decoction (GQD), a well-documented traditional Chinese Medicine (TCM) formula, was reported with convincing anti-diabetic effects in clinical practice. However, the precise antidiabetic mechanism of GQD remains unknown. In this study, the anti-hyperglycemic and/or lipid lowering effects of GQD were demonstrated in high-fat diet with a low dose of streptozotocin induced diabetic Sprague-Dawley rats and insulin resistance (IR)-3T3-L1 adipocytes. GQD treatment increased expression and activity levels of both PPAR? and PPAR? in adipocytes, which transcriptionally affected an ensemble of glucose and lipid metabolic genes in vivo and in vitro. The results clearly indicated that GQD treatment intervened with multiple pathways controlled by concomitantly downstream effects of adipocytic PPAR? and PPAR?, to influence two opposite lipid pathways: fatty acid oxidation and lipid synthesis. Antagonist GW9662 decreased the mRNA expression of Ppar? and target genes Adpn and Glut4 whereas GW6471 decreased the mRNA expression of Ppar? and target genes Cpt-1?, Lpl, Mcad, Lcad, Acox1, etc. Nuclear location and activity experiments showed that more PPAR? and PPAR? shuttled into nuclear to increase its binding activities with target genes. GQD decreased the phosphorylation level of ERK1/2 and/or CDK5 to elevate PPAR? and PPAR? activities in IR-3T3-L1 adipocytes through post-translational modification. The increase in p-p38MAPK and SIRT1 under GQD treatment may be attributed to partially reduce PPAR? adipogenesis activity and/or activate PPAR? activity. Compared with the rosiglitazone-treated group, GQD elevated Cpt-1? expression, decreased diabetic biomarker Fabp4 expression, which produced an encouraging lipid profile with triglyceride decrease partially from combined effects on upregulated adipocytic PPAR? and PPAR? activities. These results suggested that GQD improved diabetes by intervening a diverse array of PPAR? and PPAR? upstream and downstream signaling transduction cascades, which jointly optimized the expression of target gene profiles to promote fatty acid oxidation and accelerate glucose uptake and utilization than PPAR? full agonist rosiglitazone without stimulating PPAR? activity. Thus, GQD showed anti-diabetic/or antihyperglycemic effects, partially through regulating adipocytic PPAR? and PPAR? signaling systems to maintaining balanced glucose and lipid metabolisms. This study provides a new insight into the anti-diabetic effect of GQD as a PPAR?/? dual agonist to accelerate the clinical use.

Dataset Information

Troglitazone activates TRPV1 and causes deacetylation of PPAR? in 3T3-L1 cells.

Publications

Troglitazone activates TRPV1 and causes deacetylation of PPARγ in 3T3-L1 cells.

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