Up-Regulation of PPAR-γ mRNA Expression in the Liver of Obese Patients: an Additional Reinforcing Lipogenic Mechanism to SREBP-1c Induction

Introduction: Triglyceride accumulation in the liver is an early feature in the development of nonalcoholic fatty liver disease (NAFLD) associated with human obesity, which is a multifactorial syndrome and whose underlying mechanisms are beginning to be understood. Objectives: Liver peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression was measured as a signaling mechanism related to steatosis in obese patients with NAFLD. Methods: Liver PPAR-gamma and sterol receptor element-binding protein 1c (SREBP-1c) mRNA(real-time RT-PCR), serum total adiponectin (RIA), and high molecular weight (HMW)-adiponectin (ELISA) levels, and insulin resistance (IR) evolution (homeostasis model assessment-IR) were determined in 22 obese NAFLD patients (16 with steatosis and six with steatohepatitis) who underwent subtotal gastrectomy with gastrojejunal anastomosis in Roux-en-Y and 16 nonobese subjects who underwent laparoscopic cholecystectomy (controls). Results: Liver PPAR-gamma mRNA levels were 112 and 188% higher (P < 0.05) than control values in obese patients with steatosis and steatohepatitis, respectively, who also exhibited 70 and 62% increases in those of SREBP-1c, concomitantly with IR and lower levels of serum total adiponectin and HMW-adiponectin (P < 0.05). Liver PPAR-gamma expression showed positive associations with SREBP-1c mRNA levels (r = 0.86; P < 0.0001), serum insulin levels (r = 0.39; P < 0.01), and homeostasis model assessment-IR (r = 0.60; P < 0.0001), and negative correlations with total adiponectin (r = -0.37; P < 0.01) and HMW-adiponectin (r = -0.51; P < 0.001) levels in serum. Conclusions: PPAR-gamma is up-regulated in the liver of obese patients with NAFLD, representing an additional reinforcing lipogenic mechanism to SREBP-1c induction in the development of hepatic steatosis. (J Clin Endocrinol Metab 96: 1424-1430, 2011)