Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: The preventing overweight using novel dietary strategies (POUNDS LOST) trial

Min Xu, Qibin Qi, Jun Liang, George A. Bray, Frank B. Hu, Frank M. Sacks, Lu Qi

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Background-Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/ aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial. Methods and Results-We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ≤0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the highfat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ≤ 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group (P=0.02 and P=0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss (P=0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain. Conclusions-Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet.

Original languageEnglish (US)
Pages (from-to)1283-1289
Number of pages7
JournalCirculation
Volume127
Issue number12
DOIs
StatePublished - Mar 26 2013
Externally publishedYes

Keywords

  • Branched-chain amino acids
  • Gene-diet interaction
  • Insulin resistance
  • Weight loss

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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