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

• Published in: Circulation research Vol. 100; no. 7; pp. 1063 - 1070
• Main Authors: Zhang, Li Li, Liu, Dao Yan, Ma, Li Qun, Luo, Zhi Dan, Cao, Ting Bing, Zhong, Jian, Yan, Zhen Cheng, Wang, Li Juan, Zhao, Zhi Gang, Zhu, Shan Jun, Schrader, Mark, Thilo, Florian, Zhu, Zhi Ming, Tepel, Martin
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 13.04.2007; Lippincott
• Subjects: 3T3-L1 Cells; Adipocytes - metabolism; Adipogenesis; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Calcium - metabolism; Capsaicin - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, Obese; Obesity; Obesity - prevention & control; RNA, Small Interfering - pharmacology; Stem Cells - metabolism; TRPV Cation Channels - agonists; TRPV Cation Channels - deficiency; TRPV Cation Channels - drug effects; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Vertebrates: cardiovascular system; Viscera; Obesity; RNAi; Nutrition disorder; Activation; transient receptor potential vanilloid type-1; Transients; Vertebrata; TRPV1 vanilloid receptor; Mammalia; TRPV1 knockout adipogenesis; Circulatory system; Mutation; Vanilloid receptor; Nutritional status
• ISSN: 0009-7330; 1524-4571; 1524-4571
• DOI: 10.1161/01.RES.0000262653.84850.8b

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-γ, 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.