DOI: 10.15146/r3sd4b
title: Mechanisms of Anti-Obesity Effects of Capsaicin

description: 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. 
description: Metabolic 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 <i>ad libitum </i>access to food and water. After
 acclimatization for 24 hr., metabolic parameters including the volume of
 carbon dioxide produced (VCO<sub>2</sub>), the volume of
 oxygen consumed (VO<sub>2</sub>), the respiratory exchange
 ratio (RER = VCO<sub>2</sub>/VO<sub>2</sub>), 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 &lt; 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.
description: 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.