title: Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms.
abstract: The growing epidemic of obesity and metabolic diseases necessitates the development of novel strategies to prevent and treat such diseases. Current research suggests that browning of white adipose tissue (WAT) promotes energy expenditure to counter obesity. Recent research suggests that activation of the TRPV1 channels counters obesity. However, the mechanism by which activation of TRPV1 channels counters obesity still remains unclear.
  
  
  
  We evaluated the effect of dietary capsaicin to induce a browning program in WAT by activating TRPV1 channels to prevent diet-induced obesity using wild-type and TRPV1(-/-) mouse models. We performed experiments using preadipocytes and fat pads from these mice.
  
  
  
  Capsaicin stimulated the expression of brown fat-specific thermogenic uncoupling protein-1 and bone morphogenetic protein-8b in WAT. Capsaicin triggered browning of WAT by promoting sirtuin-1 expression and activity via TRPV1 channel-dependent elevation of intracellular Ca(2) (+) and phosphorylation of Ca(2) (+) /calmodulin-activated protein kinase II and AMP-activated kinase. Capsaicin increased the expression of PPARγ 1 coactivator α and enhanced metabolic and ambulatory activity. Further, capsaicin stimulated sirtuin-1-dependent deacetylation of PPARγ and the transcription factor PRDM-16 and facilitated PPARγ-PRDM-16 interaction to induce browning of WAT. Dietary capsaicin did not protect TRPV1(-/-) mice from obesity.
  
  
  
  Our results show for the first time that activation of TRPV1 channels by dietary capsaicin triggers browning of WAT to counteract obesity. Our results suggest that activation of TRPV1 channels is a promising strategy to counter obesity.
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY, USA.
authors.forename: Padmamalini
authors.initials: P
authors.lastname: Baskaran
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY, USA.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thyagarajan
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000819:agonists* / Q000172:deficiency / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin