title: CTSK inhibitor exert its anti-obesity effects through regulating adipocyte differentiation in high-fat diet induced obese mice.
abstract: Obesity is associated with increased risk of developing numerous adverse health conditions. Cathepsin k (CTSK) is highly expressed in adipose tissues of obese patients and animal models. Although CTSK has been demonstrated to promote adipocyte differentiation in 3T3-L1 cells, the effects of CTSK selective inhibitor (CKSI) on weight gain and insulin resistance have not been well examined. High-fat diet (HFD) induced obese male C57BL/6 mice were fed a diet with or without CKSI for 8 weeks. The HFD induced increase in adipose tissue weight gain, increase in homeostasis model assessment (HOMA) index as well as accumulation of large adipocytes. After CKSI treatment, all these effects were blunted compared with the HFD control group. A study of the mechanism demonstrated a role for CKSI in significantly down-regulating the expression of two key transcription factors, peroxisome proliferators-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are markers of adipogenic differentiation. These results indicated that the CKSI possesses an anti-obesity effect, possibly involving the inhibition of adipocyte differentiation. CTSK is likely to be a new target of therapeutic intervention for the treatment of obesity.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Weibin
authors.initials: W
authors.lastname: Xu
authors.forename: Junxi
authors.initials: J
authors.lastname: Lu
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D056657:Cathepsin K; C534132:Ctsk protein, mouse