Mechanisms of Anti-Obesity Effects of Capsaicin

Obesity is a major metabolic disease. Currently, there are no effective strategies to counter obesity. Transient receptor potential vanilloid subfamily 1 (TRPV1), a non-selective cation channel protein expressed in metablically important tissues, has been pursued as a target to combat obesity. In our efforts to understand the mechanisms by which activation of TRPV1 by its selective agonist capsaicin counters obesity we discovered that mammalian white and brown adipose tissues (WAT and BAT, respectively) endgenously express TRPV1 protein. Feeding a high fat diet suppressed the expression of TRPV1 in both WAT and BAT. Feeding capsaicin along with high fat diet countered this, prevented obesity and promoted weight loss by 1). triggering the conversion of WAT to beige like phenotype, which expresses enhanced thermogenic UCP-1 and BMP compared to WAT. 2). enhancing thermogenesis in BAT and suppressing high fat diet-induced hypertension, hyperlipidemia and glucose intolerance. Also, capsaicin stimulates the deacetylation and interaction of PPAR gamma and PRDM-16 in both WAT and BAT by activating the metabolic sensor sirtuin-1. Further studies analyzing the molecular mechanisms underlying these processes and developing TRPV1 agonists as novel anti-obesity agents are in progress.These data sets were collected using normal chow or high fat diet (60% calories from fat) +/- capsaicin (0.01% in total high fat diet). The data were collected after feeding mice with the respective diets for 32 weeks. Funding provided by: American Heart AssociationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000968Award Number: 15BGIA23250030Metabolic activity was determined by using the Comprehensive Laboratory Animal Monitoring System [CLAMS™, Columbus Instruments, Columbus, OH, USA (Ren, 2004; Turdi, Kandadi, Zhao, Huff, Du & Ren, 2011)]. Mice were individually placed in the CLAMS metabolic cages with ad libitum access to food and water. After acclimatization for 24 hr., metabolic parameters including the volume of carbon dioxide produced (VCO2), the volume of oxygen consumed (VO2), the respiratory exchange ratio (RER = VCO2/VO2), the caloric (heat) value and ambulatory activity were determined for 48 hr. Heat production was calculated by using modified Weir equation [(Moudiou, Galli-Tsinopoulou, Vamvakoudis & Nousia-Arvanitakis, 2007); Metabolic rate = (3.941*VO2 + 1.106*VCO2)/100] (Smyrnios, Curley & Shaker, 1997). The data (xl file format) was collected for each mouse and the data were averaged and statistically analyzed to calculate the mean, SEM and staistuical significance amojng groups (** P < 0.01). These data were published as peer reviewed articles. We also measured te expression of thermogenic genes in the inguinal and brown fat of wild type and TRPV1 knockout mice that were fed normal chow or high fat diet (+/- capsaicin) by quantitative RT-PCR method. Subcutaneous (inguinal) white adipose tissue (sWAT) and brown adipose tissue (BAT) fat pads collected from WT mice-fed NCD (± CAP)-fed for 32 weeks were collected and used for quantitative RT-PCR experiments. Each experiment was performed in duplicates for statistical analysis. Total RNA was isolated using Tri-reagent (Sigma, USA) according to manufacturer's instructions and cDNA was synthesized using Quantitect reverse transcription kit (Qiagen, Valencia, CA) using Q5plex PCR system (Qiagen Valencia, CA). Real -time PCR was performed using Quantitect SYBR green PCR kit on Q5plex system. 18s mRNA was used as the reference gene. Amplification was performed using 20-µl-reaction volume according to manufacturer's instruction