title: Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes.
abstract: OBJECTIVE
  Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending "brite" cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of "brite" phenotype during differentiation of 3T3-L1 preadipocytes.
  
  
  METHODS
  Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin.
  
  
  RESULTS
  TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1-100 µM, capsaicin promotes expression of major pro-adipogenic factor PPARγ and some of its downstream targets. In concentrations of 1 µM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight.
  
  
  CONCLUSIONS
  Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher doses.
authors: National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India.
authors: Ritesh K
authors: RK
authors: Baboota
authors: National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India.
authors: Dhirendra P
authors: DP
authors: Singh
authors: National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India.
authors: Siddhartha M
authors: SM
authors: Sarma
authors: Department of Biotechnology, University Institute of Engineering and Technology (UIET), Panjab University, Chandigarh, India.
authors: Jaspreet
authors: J
authors: Kaur
authors: Department of Biochemistry, Panjab University, Chandigarh, India.
authors: Rajat
authors: R
authors: Sandhir
authors: Department of Biochemistry, Panjab University, Chandigarh, India.
authors: Ravneet K
authors: RK
authors: Boparai
authors: National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India.
authors: Kanthi K
authors: KK
authors: Kondepudi
authors: National Agri-Food Biotechnology Institute (NABI), SAS Nagar, Punjab, India.
authors: Mahendra
authors: M
authors: Bishnoi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D059305:Diet, High-Fat; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010641:Phenotype; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D054392:Adipokines; D015415:Biomarkers; D047495:PPAR gamma; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C071423:capsazepine; D002211:Capsaicin