Intraperitoneal administration attenuates thiazolidinedione-induced hepatic steatosis in KKAy mice with increased hepatic peroxisome proliferator-activated receptor (PPAR)γ mRNA expression
| Autor: | Junya Oribe, Hironobu Yoshimatsu, Tetsuya Kakuma, Miwa Haranaka, Kenjirou Okamoto, Masataka Seike |
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| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
medicine.medical_specialty Nutrition and Dietetics business.industry medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Intraperitoneal injection Fatty liver Adipose tissue Peroxisome proliferator-activated receptor White adipose tissue medicine.disease Endocrinology chemistry Internal medicine medicine Thiazolidinedione Steatosis business Pioglitazone medicine.drug |
| Zdroj: | Obesity researchclinical practice. 6(3) |
| ISSN: | 1871-403X |
| Popis: | Summary 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 50mg/kg/day worsened the hepatic steatosis in KKAy mice, however, the treatment at 50mg/kg/day was not worse than that at 15mg/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 15mg/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. |
| Databáze: | OpenAIRE |
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