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

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 5; pp. 1424 - 1430
• Main Authors: Pettinelli, Paulina, Videla, Luis A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.05.2011; Copyright by The Endocrine Society
• Subjects: Adiponectin; Adiponectin - biosynthesis; Adiponectin - blood; Adult; Anastomosis; Anastomosis, Roux-en-Y; Biological and medical sciences; Blood; Cholecystectomy; Diseases; Endocrinopathies; Enzyme-linked immunosorbent assay; Evolution; Fatty liver; Fatty Liver - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastrectomy; Gene expression; Homeostasis; Hormones; Humans; Insulin; Insulin Resistance - physiology; Laparoscopy; Liver; Liver - metabolism; Male; Measurement; Medical sciences; Molecular modelling; Molecular Weight; Obesity; Obesity - metabolism; Obesity - surgery; Patients; Peroxisome proliferator-activated receptors; Polymerase chain reaction; PPAR gamma - biosynthesis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; steatosis; Sterol Regulatory Element Binding Protein 1 - biosynthesis; Sterols; Triglycerides; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Weight; Human; Obesity; Nutrition; Digestive system; Induction; Liver; Nutrition disorder; Peroxisome proliferator activated receptor gamma; Patient; Metabolic diseases; Gene expression; Mechanism; Regulation(control); Messenger RNA; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-2129

PPAR-γ up-regulation in the liver of obese patients with nonalcoholic fatty liver disease represents an additional complementary 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-γ (PPAR-γ) mRNA expression was measured as a signaling mechanism related to steatosis in obese patients with NAFLD. Methods: Liver PPAR-γ 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-γ 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-γ 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-γ 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.