RIP140 Gene and Protein Expression Levels are Downregulated in Visceral Adipose Tissue in Human Morbid Obesity

Abstract

Receptor-interacting protein 140 (RIP140) is a corepressor for nuclear receptors with an important role in the inhibition of energy expenditure. Rip140-knockout mice are lean and resistant to diet-induced obesity due to an increase in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. The aim of the present work was to evaluate the effect of morbid obesity on gene and protein expression levels of RIP140 in visceral adipose tissue (VAT). VAT biopsies obtained from 17 subjects were used in the study. Patients were classified as lean (body mass index [BMI]=21.8+/-1.3 kg/m2) or obese (BMI=48.2+/-2.6 kg/m2). Reverse transcription polymerase chain reaction and Western blot analyses were performed to quantify the expression levels of RIP140 in VAT. We also analyzed glucose and lipid profile as well as some inflammatory factors. Obese patients exhibited significantly lower RIP140 mRNA expression levels compared to lean subjects (lean=1.00+/-0.17 arbitrary units, obese=0.65+/-0.18 arbitrary units; P<0.05). Protein expression of RIP140 followed the same trend, being significantly higher in lean volunteers (lean=1.00+/-0.18 arbitrary units, obese=0.45+/-0.11 arbitrary units; P<0.05). Furthermore, a significant negative correlation was found between RIP140 protein levels and both BMI (rho=-0.85; P<0.001) and body fat percentage (rho=-0.88; P<0.001). The lower gene and protein expression levels of RIP140 in obese subjects may suggest a compensatory mechanism in order to favor energy expenditure and reduce fat accumulation in obesity states.