title: Role of glucose-dependent insulinotropic polypeptide in adipose tissue inflammation of dipeptidylpeptidase 4-deficient rats.
abstract: OBJECTIVE
  Dipeptidyl peptidase 4 (DPP4) inhibitors, used in obese diabetic patients, reduce inflammation in several models. The role of chronic DPP4-deficiency (DPP4-) in diet-induced obesity with respect to insulin sensitivity and adipose tissue inflammation was investigated.
  
  
  METHODS
  Insulin resistance was induced by 2 months high fat diet (HFD). In vitro effects of glucose-dependent insulinotropic polypeptide (GIP) were assessed in adipose tissue explants and stromal vascular fraction (SVF).
  
  
  RESULTS
  HFD-fed DPP4-rats gained significantly more weight and visceral fat mass, yet were more insulin sensitive. Adipose tissue of DPP4- rats demonstrated increased adipocyte maturation and increased expression of enzymes involved in triglyceride uptake and synthesis, yet increased adiponectin mRNA, reduced mRNA of proinflammatory cytokines and reduced vascular adhesion molecules, suggesting reduced inflammation. In vitro and in vivo experiments explored the role of GIP in inducing this phenotype. Indeed, we demonstrated that GIP directly enhanced adiponectin expression in rat and human adipose tissue explants and in SVF. Lastly, GIP administration to normal or HFD-fed rats elevated serum adiponectin and improved their glucose tolerance test.
  
  
  CONCLUSIONS
  In a HFD model, DPP4-rats exhibited reduced adipose tissue inflammation and improved insulin resistance, which may be mediated in part by GIP induction of adiponectin.
authors: The Research Center for Digestive Tract and Liver Diseases, The Department of Gastroenterology and Liver diseases, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Shani
authors: S
authors: Ben-Shlomo
authors: Isabel
authors: I
authors: Zvibel
authors: Chen
authors: C
authors: Varol
authors: Lior
authors: L
authors: Spektor
authors: Amir
authors: A
authors: Shlomai
authors: Erwin M
authors: EM
authors: Santo
authors: Zamir
authors: Z
authors: Halpern
authors: Ran
authors: R
authors: Oren
authors: Sigal
authors: S
authors: Fishman
mesh_terms: D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D015434:Panniculitis / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic
chemical_list: D008055:Lipids; D005749:Gastric Inhibitory Polypeptide; D018819:Dipeptidyl Peptidase 4