TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet.
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.
Grau
Katrine
K
Institute of Preventive Medicine Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark. kg@ipm.regionh.dk
Cauchi
Stephane
S
Holst
Claus
C
Astrup
Arne
A
Martinez
J Alfredo
JA
Saris
Wim H M
WH
Blaak
Ellen E
EE
Oppert
Jean-Michel
JM
Arner
Peter
P
Rössner
Stephan
S
Macdonald
Ian A
IA
Klimcakova
Eva
E
Langin
Dominique
D
Pedersen
Oluf
O
Froguel
Philippe
P
Sørensen
Thorkild I A
TI
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
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