title: TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet.
abstract: BACKGROUND
  Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion.
  
  
  OBJECTIVE
  The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, low-carbohydrate: 40-45% of energy as fat (HF); compared with low-fat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (-600 kcal/d).
  
  
  METHODS
  European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-beta), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146.
  
  
  RESULTS
  Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Deltaweight) (2.6 kg; P = 0.009; n = 622), smaller DeltaFFM (1.6 kg; P = 0.027; n = 609), smaller DeltaWC (3.3 cm; P = 0.010; n = 608), and a smaller DeltaHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with DeltaREE, DeltaFatOx, DeltaHOMA-beta, or dropout.
  
  
  CONCLUSIONS
  Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.
authors.affiliation: Institute of Preventive Medicine Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark. kg@ipm.regionh.dk
authors.forename: Katrine
authors.initials: K
authors.lastname: Grau
authors.forename: Stephane
authors.initials: S
authors.lastname: Cauchi
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Oppert
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Stephan
authors.initials: S
authors.lastname: Rössner
authors.forename: Ian A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: Eva
authors.initials: E
authors.lastname: Klimcakova
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D001481:Basal Metabolism / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D016009:Chi-Square Distribution; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004038:Diet, Reducing / Q000379:methods*; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy* / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D004247:DNA