Activation of Transient Receptor Potential Vanilloid Type-1 Channel Prevents Adipogenesis and Obesity

Abstract

Abstract-We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator-activated receptor-␥, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated 3T3-L1-preadipocytes. RNA interference knockdown of TRPV1 in 3T3-L1-preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated 3T3-L1-preadipocytes was no longer prevented. During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese db/db and ob/ob mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity. Key Words: transient receptor potential vanilloid type-1 Ⅲ RNAi Ⅲ TRPV1 knockout adipogenesis Ⅲ obesity V isceral obesity as clinically assessed by waist circumference depends on the proliferation and growth of preadipocytes which is closely regulated by several genes and extracellular factors. 1-3 Among these factors capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide) has been shown to affect lipid metabolism and obesity. 4,5 However, the underlying mechanisms by which capsaicin affect visceral adipose tissue have not been completely clarified yet. Recent studies indicated that capsaicin activates the transient receptor potential vanilloid type-1 (TRPV1) channel. 6 -8 The capsaicin receptor TRPV1 belongs to the family of nonselective cation channels with high calcium permeability. 9 Now, we tested the hypothesis that capsaicin-induced activation of TRPV1 in preadipocytes prevents adipogenesis and obesity. We showed that the activation of TRPV1 channels by capsaicin increased cytosolic calcium and prevented adipogenesis of preadipocytes in vitro. The effects of capsaicin on adipogenesis were attenuated after TRPV1 knockdown. Furthermore, ...

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

“…However, TRPV1 has recently been reported to play different roles in many types of cells and tissues. Besides the involvement of TRPV1 in adipogenesis and vascular relaxation [11][12], TRPV1 in neurons and smooth muscle plays opposite functional roles in the tissue-specific regulation of microvascular diameter [35]. The present study reveals for the first time that chronic TRPV1 activation induces PGC-1α expression and improves mitochondrial function in a Ca 2+ -dependent manner in the skeletal muscle.…”

“…TRPV1 was selectively silenced with RNAi using a lentiviral system according to a previously published technique [11]. DNA templates for synthesizing silencing RNA were cloned into an expression plasmid for subsequent transfection.…”

“…TRPV1 is also present in nonneuronal tissues, such as adipose tissue and skeletal muscle [9,10]. Our previous study showed that capsaicin inhib-ited adipogenesis through a TRPV1-mediated Ca 2+ influx in adipocytes and chronic capsaicin administration prevented obesity in mice [11]. More recently, we showed that TRPV1 activation by dietary capsaicin improved endothelium-dependent vasorelaxation and regulated blood pressure in rats [12].…”

TRPV1 Agonist Monoacylglycerol Increases UCP1 Content in Brown Adipose Tissue and Suppresses Accumulation of Visceral Fat in Mice Fed a High-Fat and High-Sucrose Diet

“…Dietary CAP has activated TRPV1 and prevented obesity-induced hyperglycemia and hyperlipidemia (TG or T-Cho) in previous studies, 8,22,23) although details of the mechanism are still unclear. However, it is thought that CAP activates the sympathetic nerve by activating the TRPV1-expressing sensory nerve, and that this secretes adrenaline from the adrenal gland.…”

“…The effects of suppressing an accumulation of visceral fat, increasing oxygen consumption and promoting thermogenesis by CAP were canceled in TRPV1 knockout mice. 8,9) We searched in our previous study for the food compound which would activate TRPV1 as the functional compound increasing energy expenditure, and identified 1-or 2-monoacylglycerols (MGs) having oleic, linoleic, and -linolenic acids from wheat flour, onion (Allium cepa) and myoga (Zingiber mioga) as TRPV1 agonists. 10) The potency and efficacy of these MGs for activating TRPV1 were respectively about 50 times weaker than and half that of CAP.…”