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.
Highlights
The increasing prevalence of obesity and its associated comorbidities globally draws attention to the need for developing effective treatment or prevention strategies
Confluent 3T3-L1 pre-adipocytes were differentiated in presence of different doses of capsaicin (0.1, 0.5, 1, 10, 50 and 100 mM), RTX (200 nM and 1 mM) and capsazepine (1, 10 and 20 mM) in the differentiation media followed by maintenance media
Expression levels of selected transient receptor potential (TRP) channels were studied in preadipocytes and in adipocytes at early and late phases of adipocyte differentiation (Figure 2A)
Summary
The increasing prevalence of obesity and its associated comorbidities globally draws attention to the need for developing effective treatment or prevention strategies. A bioactive component of chili peppers and a TRPV1 agonist, has been reported to promote the process of thermogenesis [1], [2]. There is an established link between capsaicin ingestion and body weight regulation where studies indicate that capsaicin suppresses appetite and increases thermogenesis as well as energy expenditure in both rodents and human. In long term feeding experiments, dietary capsaicin administration was reported to prevent weight gain in wild type mice but not in TRPV1 knockout (KO) animals [3]. A meta-analysis of 20 trials found a modest benefit of capsaicin on weight loss via an increase in energy expenditure [4]. Capsaicin was reported to boost thermogenesis in 50% healthy volunteers with no effect on satiety [5]
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