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).

DESIGN:

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.

CONCLUSION:

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: Katrine Grau, Stephane Cauchi, Claus Holst, Arne Astrup, J Alfredo Martinez, Wim H M Saris, Ellen E Blaak, Jean-Michel Oppert, Peter Arner, Stephan Rössner, Ian A Macdonald, Eva Klimcakova, Dominique Langin, Oluf Pedersen, Philippe Froguel, Thorkild I A Sørensen
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 91 Issue 2 Pg. 472-9 (Feb 2010) ISSN: 1938-3207 [Electronic] United States
• PMID: 20032493 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dietary Carbohydrates
• Dietary Fats
• Insulin
• TCF Transcription Factors
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• DNA

Topics

• Adult
• Basal Metabolism (genetics, physiology)
• Blood Glucose (analysis)
• Chi-Square Distribution
• DNA (chemistry, genetics)
• Diet, Reducing (methods)
• Dietary Carbohydrates (administration & dosage, metabolism)
• Dietary Fats (administration & dosage, metabolism)
• Female
• Genotype
• Humans
• Insulin (genetics)
• Male
• Middle Aged
• Obesity (diet therapy, genetics, metabolism)
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• TCF Transcription Factors (genetics, metabolism)
• Transcription Factor 7-Like 2 Protein