title: Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ influx.
abstract: BACKGROUND
  The prevalence of obesity has dramatically increased worldwide and has attracted rising attention, but the mechanism is still unclear. Previous studies revealed that transient receptor potential vanilloid 1 (TRPV1) channels take part in weight loss by enhancing intracellular Ca2+ levels. However, the potential mechanism of the effect of dietary capsaicin on obesity is not completely understood. Ca2+ transfer induced by connexin43 (Cx43) molecules between coupled cells takes part in adipocyte differentiation. Whether TRPV1-evoked alterations in Cx43-mediated adipocyte-to-adipocyte communication play a role in obesity is unknown.
  
  
  METHODS
  We investigated whether Cx43 participated in TRPV1-mediated adipocyte lipolysis in cultured 3T3-L1 preadipocytes and visceral adipose tissues from humans and wild-type (WT) and TRPV1-deficient (TRPV1-/-) mice.
  
  
  RESULTS
  TRPV1 and Cx43 co-expressed in mesenteric adipose tissue. TRPV1 activation by capsaicin increased the influx of Ca2+ in 3T3-L1 preadipocytes and promoted cell lipolysis, as shown by Oil-red O staining. These effects were deficient when capsazepine, a TRPV1 antagonist, and 18 alpha-glycyrrhetinic acid (18α-GA), a gap-junction inhibitor, were administered. Long-term chronic dietary capsaicin reduced the weights of perirenal, mesenteric and testicular adipose tissues in WT mice fed a high-fat diet. Capsaicin increased the expression levels of p-CaM, Cx43, CaMKII, PPARδ and HSL in mesenteric adipose tissues from WT mice fed a high-fat diet, db/db mice, as well as obese humans, but these effects of capsaicin were absent in TRPV1-/- mice. Long-term chronic dietary capsaicin decreased the body weights and serum lipids of WT mice, but not TRPV1-/- mice, fed a high-fat diet.
  
  
  CONCLUSIONS
  This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+ influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral fat remodeling through the up-regulation of Cx43.
authors: Jian
authors: J
authors: Chen
authors: Li
authors: L
authors: Li
authors: Yingsha
authors: Y
authors: Li
authors: Xia
authors: X
authors: Liang
authors: Qianqian
authors: Q
authors: Sun
authors: Hao
authors: H
authors: Yu
authors: Jian
authors: J
authors: Zhong
authors: Yinxing
authors: Y
authors: Ni
authors: Jing
authors: J
authors: Chen
authors: Zhigang
authors: Z
authors: Zhao
authors: Peng
authors: P
authors: Gao
authors: Bin
authors: B
authors: Wang
authors: Daoyan
authors: D
authors: Liu
authors: Zhiming
authors: Z
authors: Zhu
authors: Zhencheng
authors: Z
authors: Yan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000008:administration & dosage*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin; D002118:Calcium