Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-Ay mice.

摘要: Pathogenesis of metabolic syndrome–related nonalcoholic steatohepatitis (NASH) involves abnormal tissue-repairing responses in the liver. We investigated effect pioglitazone, a thiazolidinedione derivative (TZD), on hepatic regenerative obese, diabetic KK-Ay mice. Male mice 9 weeks after birth underwent two-thirds partial hepatectomy (PH) repeated intragastric injections pioglitazone (25 mg/kg) for 5 days. Almost half died within 48 hours PH;however, mortality was completely prevented pretreated with pioglitazone. In mice, bromodeoxyuridine (BrdU) incorporation to hepatocyte nuclei PH reached only 1%; however, pretreatment significantly increased BrdU-positive cells 8%. Cyclin D1 barely detectable PH. contrast, overt expression cyclin observed 24 Hepatic tumor necrosis factor alpha (TNF-α) messenger RNA (mRNA) tremendously 1 hour levels reaching ninefold over C57Bl/6 given PH, whereas blunted this increase by almost three-fourths. Pioglitazone normalized hypoadiponectinemia completely. Serum interleukin (IL)-6 and leptin were elevated extensively largely decreased Indeed, aberrant increases signal transducers activators transcription (STAT)3 phosphorylation suppressor cytokine signaling (SOCS)-3 mRNA liver Conclusion: These findings indicated that improved regeneration failure The mechanism underlying most likely normalization pattern adipokines subsequent during early stage (HEPATOLOGY 2009.)