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TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet
- Grau, Katrine, Cauchi, Stephane, Holst, Claus, Astrup, Arne, Martinez, J. Alfredo, Saris, Wim HM, Blaak, Ellen E., Oppert, Jean-Michel, Arner, Peter, Rössner, Stephan, Macdonald, Ian A., Klimcakova, Eva, Langin, Dominique, Pedersen, Oluf, Froguel, Philippe, Sørensen, Thorkild IA
- TheAmerican journal of clinical nutrition 2010 v.91 no.2 pp. 472-479
- nutrition risk assessment, transcription factors, experimental diets, dietary fat, dietary carbohydrate, high fat diet, low fat diet, low carbohydrate diet, high carbohydrate diet, energy intake, obesity, diet-related diseases, nutrition-genotype interaction, glucagon-like peptides, genotype, alleles, homeostasis, body mass index, body weight, body fat, fat free mass, waist circumference, resting energy expenditure, lipid peroxidation, insulin secretion, insulin resistance, weight loss, lipolysis, randomized clinical trials, dietary energy sources, Europe
- 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-β), 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 (Δweight) (2.6 kg; P = 0.009; n = 622), smaller ΔFFM (1.6 kg; P = 0.027; n = 609), smaller ΔWC (3.3 cm; P = 0.010; n = 608), and a smaller ΔHOMA-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 ΔREE, ΔFatOx, ΔHOMA-β, 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.