A gene variation (rs12691) in the CCAT/enhancer binding protein α modulates glucose metabolism in metabolic syndrome

Nutr Metab Cardiovasc Dis. 2013 May;23(5):417-23. doi: 10.1016/j.numecd.2011.09.008. Epub 2012 Jan 23.

Abstract

Background and aims: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients.

Methods and results: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration.

Conclusion: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients.

Trial registration: ClinicalTrials.gov NCT00429195.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adult
  • Aged
  • Alleles
  • Blood Glucose / analysis
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Body Weight
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • DNA / genetics
  • DNA / isolation & purification
  • Dietary Fats / administration & dosage
  • Dietary Supplements*
  • Fasting
  • Fatty Acids / administration & dosage
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage
  • Female
  • Genotype
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Leptin / blood
  • Lipid Metabolism / genetics
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Resistin / blood
  • Triglycerides / blood

Substances

  • Adiponectin
  • Blood Glucose
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Dietary Fats
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Omega-3
  • Insulin
  • Leptin
  • Resistin
  • Triglycerides
  • DNA

Associated data

  • ClinicalTrials.gov/NCT00429195