title: The adipose tissue endocrine mechanism of the prophylactic protective effect of pioglitazone in high-fat diet-induced insulin resistance.
abstract: OBJECTIVE
  To explore the adipose tissue endocrine mechanism of pioglitazone and its possible prophylactic role in insulin resistance.
  
  
  METHODS
  Male Wistar rats were randomized to receive a normal diet (N group), a high-fat insulin resistance-inducing diet (IR group), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken. HepG2 cells were cultured with palmitic acid (PA), pioglitazone and PA plus pioglitazone, and RNA interference was used to downregulate adiponectin receptor (AdipoR) 2 in these cells. The mRNA and protein levels of adipokines (resistin and adiponectin), AdipoR1 and 2 and uptake of [3H]-labelled glucose were measured in the HepG2 cells.
  
  
  RESULTS
  Resistin and adiponectin in adipose tissue and AdipoR2 in liver tissue were significantly decreased in the IR group compared with the N group. Adiponectin and AdipoR2 were significantly increased and insulin resistance significantly decreased in the P group versus the IR group. In HepG2 cells, AdipoR2 levels and glucose uptake decreased significantly when PA was ≥200 μM, but were elevated by pioglitazone. Small interfering RNA-AdipoR2 confirmed glucose uptake in liver was regulated by AdipoR2.
  
  
  CONCLUSIONS
  Pioglitazone prevented insulin resistance in rats fed a high-fat diet. Liver AdipoR2-mediated glucose uptake is important in the prophylactic effect of pioglitazone on insulin resistance.
authors.affiliation: Department of Endocrinology, The Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Mu
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: H
authors.initials: H
authors.lastname: Tian
authors.forename: C
authors.initials: C
authors.lastname: Pan
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002554:Cerebrosides / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D000077205:Pioglitazone; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C047853:(beta-glucopyranosyl)-1-thiocerebroside; C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D002554:Cerebrosides; D007004:Hypoglycemic Agents; C499624:RETN protein, human; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D052243:Resistin; D045162:Thiazolidinediones; D019308:Palmitic Acid; D000077205:Pioglitazone