title: Intraperitoneal administration attenuates thiazolidinedione-induced hepatic steatosis in KKAy mice with increased hepatic peroxisome proliferator-activated receptor (PPAR)γ mRNA expression.
abstract: CONCLUSIONS
  
  
  
  BACKGROUND
  The pathogenesis of thiazolidinediones (TZDs)-induced hepatic steatosis in genetically obese diabetic mice has not been fully clarified. We herein examined the effects of pioglitazone treatment on liver histology.
  
  
  METHODS
  To investigate TZDs-induced hepatic steatosis, KKAy mice were treated with pioglitazone orally or by intraperitoneal injection.
  
  
  RESULTS
  Orally administered pioglitazone at 15 and/or 50 mg/kg/day worsened the hepatic steatosis in KKAy mice, however, the treatment at 50 mg/kg/day was not worse than that at 15 mg/kg/day. The basal expression of peroxisome proliferator-activated receptor (Ppar)γ mRNA in the liver was upregulated to approximately 10% of that in white adipose tissue in these mice. Although no induction of hepatic Pparg mRNA by pioglitazone treatment was observed, the mRNA expression of the downstream lipogenic enzymes significantly increased. On the other hand, intraperitoneal administration of 15 mg/kg/day did not lead to deterioration of the hepatic steatosis of KKAy mice. Moreover, intraperitoneal administration led to an accompanying shift of fat distribution from intra-abdominal to subcutaneous adipose depots, and further increases in the serum adiponectin levels. In addition, a 5 day treatment without any change in body weight led to an obvious improvement in hepatic steatosis.
  
  
  CONCLUSIONS
  Intraperitoneal administration of pioglitazone can act more strongly on intra-abdominal adipose tissues, and attenuates TZDs-induced hepatic steatosis in KKAy mice. The present study suggests that hepatic steatosis due to chronic treatment with TZDs is affected by the balance between endogenous lipogenesis in the liver and the lipid storage in adipose tissues, both occurring through PPARγ.
authors: Junya
authors: J
authors: Oribe
authors: Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan. Electronic address:kakuma@oita-u.ac.jp.
authors: Tetsuya
authors: T
authors: Kakuma
authors: Miwa
authors: M
authors: Haranaka
authors: Kenjirou
authors: K
authors: Okamoto
authors: Masataka
authors: M
authors: Seike
authors: Hironobu
authors: H
authors: Yoshimatsu