TNF-α promoter methylation as a predictive biomarker for weight-loss response

Abstract

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine which is commonly elevated in obese subjects and whose promoter is susceptible to be regulated by cytosine methylation. The aim of this research was to analyze whether epigenetic regulation of human TNF-α promoter by cytosine methylation could be involved in the predisposition to lose body weight after following a balanced hypocaloric diet. Twenty-four patients (12 women/12 men) with excessive body weight-for-height (BMI: 30.5 0.32 kg/m 2; age: 34 4 years old) followed an 8-week energy-restricted diet. Blood mononuclear cell DNA, isolated before the nutritional intervention, was treated with bisulfite and a region of TNF-α gene promoter (from 360 to 50 bp) was sequenced. Obese men with successful weight loss (5% of initial body weight) showed lower levels of total TNF-α promoter methylation (r = 0.74; P = 0.021), especially in the positions 170 bp (r = 0.75, P = 0.005) and 120 bp (r = 0.70, P = 0.011). Baseline TNF-α circulating levels were positively associated with total promoter methylation (r = 0.84, P = 0.005) and methylation at position 245 bp (r = 0.75, P = 0.020). TNF-α promoter methylation could be a good inflammation marker predicting the hypocaloric diet-induced weight-loss, and constitutes a first step toward personalized nutrition based on epigenetic criteria.