Journal of Physiology and Biochemistry

, Volume 67, Issue 3, pp 463–470 | Cite as

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

  • Paul Cordero
  • Javier Campion
  • Fermin I. Milagro
  • Estibaliz Goyenechea
  • Thais Steemburgo
  • Biola M. Javierre
  • J. Alfredo Martinez
Original Paper


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.


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


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Copyright information

© University of Navarra 2011

Authors and Affiliations

  • Paul Cordero
    • 1
  • Javier Campion
    • 1
  • Fermin I. Milagro
    • 1
  • Estibaliz Goyenechea
    • 2
  • Thais Steemburgo
    • 3
  • Biola M. Javierre
    • 4
  • J. Alfredo Martinez
    • 1
  1. 1.Department of Nutrition and Food Sciences, Physiology and ToxicologyUniversity of NavarraPamplonaSpain
  2. 2.Donostia HospitalSan SebastianSpain
  3. 3.Endocrine Division, Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC)Bellvitge Biomedical Research Institute (IBIDELL)BarcelonaSpain

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