Capsaicin Induces “Brite” Phenotype in Differentiating 3T3-L1 Preadipocytes

Abstract

ObjectiveTargeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending “brite” cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of “brite” phenotype during differentiation of 3T3-L1 preadipocytes.MethodsMultiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin.Results TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1–100 µM, capsaicin promotes expression of major pro-adipogenic factor PPARγ and some of its downstream targets. In concentrations of 1 µM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight.ConclusionOur findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher doses.

MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance

“…Activation of gastrointestinal TRPV1 receptors by capsaicin increases central sympathetic stimulation of BAT (120). Capsaicin also acts directly on TRPV1 receptors in adipose tissue (121), increasing expression of brown adipocytes marker genes in differentiating 3T3-L1 preadipocytes in vitro (122).…”

Role of Thermo-Sensitive Transient Receptor Potential Channels in Brown Adipose Tissue

“…58) Opposite results were also reported and showed that treatment with capsaicin in the late stage slightly increased expression levels of fatty acid-binding protein 4 (Fabp4), Pparγ2, and peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) in the HB2 brown adipocyte cell line. 55,59) Pharmacological inhibition of TRPV1 activity also enhanced expression levels of Pgc-1α mRNA, which is a key transcriptional coregulator of oxidative metabolism and thermogenesis. 60) In addition, activation of TRPV1 by capsaicin up-regulates expression of thermogenic genes and induces the "browning" phenotype in differentiating 3T3-L1 pre-adipocytes ( Fig.…”

Role of n-3 Polyunsaturated Fatty Acids in Ameliorating the Obesity-Induced Metabolic Syndrome in Animal Models and Humans

“…Even though the UCP1 level is lower in these cells than in the classic brown adipocytes, thermogenesis can also be induced by appropriate stimulation, such as environmental conditions (e.g., the cold) or nutrients (e.g., capsaicin, curcumin, fish oils) [43,44,45]. Furthermore, the mitochondrial respiration and energy expenditure can be similar to that of brown adipocytes [38,46].…”