title: The dipeptidyl peptidase-4 inhibitor des-fluoro-sitagliptin regulates brown adipose tissue uncoupling protein levels in mice with diet-induced obesity.
abstract: OBJECTIVE
  Dipeptidyl peptidase (DPP)-4 is responsible for the degradation of several peptides that contain an alanine or proline at the penultimate position or position P1. DPP-4 inhibitors (DPP-4is) have protective effects against type-2 diabetes and several metabolic disorders.
  
  
  METHODS
  In the present study, we examined the effects of des-fluoro-sitagliptin (DFS), a DDP-4i, on body adiposity and levels of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ coactivator-1 (PGC-1), and uncoupling proteins (UCPs) in mice with diet-induced obesity.
  
  
  RESULTS
  Treatment with DFS dose-dependently decreased the weight of white adipose tissue and serum levels of glucose, compared with controls, without influencing food intake (P<0.05). Additionally, DFS treatment increased the levels of PPAR-α, PGC-1, and UCPs in brown adipose tissue (BAT), and of PPAR-α and UCP3 in skeletal muscle (P<0.05). Furthermore, the effects on BAT PGC-1 and muscle PPAR-α levels were attenuated by treatment with the glucagon-like peptide 1 (GLP-1) antagonist exendin (9-39). Interestingly, hypothalamic levels of proopiomelanocortin (POMC) were increased by DFS treatment and the effects of DFS on PPAR-α, PGC-1, and UCP levels were attenuated in melanocortin (MC)-4 receptor-deficient mice.
  
  
  CONCLUSIONS
  In conclusion, high-dose DFS appeared to regulate body adiposity and UCPs in mice with diet-induced obesity, at least partly through a GLP-1 and/or MC-4 pathway.
authors.affiliation: Department of Internal Medicine 1, Faculty of Medicine, Oita University, Yufu, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Mitsutomi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ueno
authors.forename: Koro
authors.initials: K
authors.lastname: Gotoh
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kakuma
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*; D000071256:Uncoupling Protein 1
chemical_list: D004041:Dietary Fats; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D011719:Pyrazines; D014230:Triazoles; D000071256:Uncoupling Protein 1; D000068900:Sitagliptin Phosphate