Original Paper

Journal of Physiology and Biochemistry

, Volume 67, Issue 3, pp 463-470

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

  • Paul CorderoAffiliated withDepartment of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra
  • , Javier CampionAffiliated withDepartment of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra
  • , Fermin I. MilagroAffiliated withDepartment of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra
  • , Estibaliz GoyenecheaAffiliated withDonostia Hospital
  • , Thais SteemburgoAffiliated withEndocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul
  • , Biola M. JavierreAffiliated withChromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IBIDELL)
  • , J. Alfredo MartinezAffiliated withDepartment of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Obesity-associated adipose tissue enlargement is characterized by an enhanced proinflammatory status and an elevated secretion of adipokines such as leptin and cytokines such as tumor necrosis factor (TNF)-alpha. Among the different mechanisms that could underlie the interindividual differences in obesity, epigenetic regulation of gene expression has emerged as a potentially important determinant. Therefore, 27 obese women (age, 32–50 years; baseline body mass index, 34.4 ± 4.2 kg/m2) were prescribed an 8-week low-calorie diet, and epigenetic marks were assessed. Baseline and endpoint anthropometric parameters were measured, and blood samples were drawn. Genomic DNA and RNA from adipose tissue biopsies were isolated before and after the dietary intervention. Leptin and TNF-alpha promoter methylation were measured by MSP after bisulfite treatment, and gene expression was also analyzed. Obese women with a successful weight loss (≥5% of initial body weight, n = 21) improved the lipid profile and fat mass percentage (−12%, p < 0.05). Both systolic (−5%, p < 0.05) and diastolic (−8%, p < 0.01) blood pressures significantly decreased. At baseline, women with better response to the dietary intervention showed lower promoter methylation levels of leptin (−47%, p < 0.05) and TNF-alpha (−39%, p = 0.071) than the non-responder group (n = 6), while no differences were found between responder and non-responder group in leptin and TNF-alpha gene expression analysis. These data suggest that leptin and TNF-alpha methylation levels could be used as epigenetic biomarkers concerning the response to a low-calorie diet. Indeed, methylation profile could help to predict the susceptibility to weight loss as well as some comorbidities such as hypertension or type 2 diabetes.

Keywords

DNA methylation Epigenetic biomarker Obesity Low-calorie diet TNF-alpha Leptin