How is "BMI Reduction in Response to Low-fat Diet" encoded by the genome?
According to the World Health Organization (WHO), the number of patients with type 2 diabetes has been increasing, and the trend is even greater in n low- and middle-income countries. Because TCF7L2 gene variants have been found to be associated with an increased risk of type 2 diabetes, it might be important to investigate if these variants modulate the efficacy of dietary intervention for body composition.
A recent randomized trial reported that obese individuals with the TCF7L2 single nucleotide polymorphism (SNP) rs7903146 risk allele have better responses in weight loss and obesity outcomes after 10 weeks of consumption of a low-fat, but not high-fat, dietary intervention. In addition, the study suggested that individuals who carry TCF7L2 risk alleles are more sensitive to low-fat than high-fat weight-loss diets; however, the intervention period was short. Thus, researchers aimed to investigate whether TCF7L2 genotypes of the well-recognized SNPs rs7903146 and rs12255372, which are in moderate linkage disequilibrium (LD) in European populations, modulate the response to diets of different fat content in relation to long-term changes in anthropometric measures and body composition in a 2-year randomized, weight-loss intervention trial.
Researchers analyzed data in the Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial, which is a 2-year weight-loss randomized clinical trial of diets that differed in macronutrient proportions. As a part of the trial, participants were genotyped for TCF7L2 gene polymorphisms to investigate the impact of the variants on the efficacy of dietary interventions on body composition. The polymorphisms were selected for the analysis because TCF7L2 variants have been associated with an increased risk of type 2 diabetes and higher adiposity. Participants (n=591) were randomly assigned to 4 energy-reduced diets groups with the following goals for total fat, protein, and carbohydrate as percentages of total energy: 20%, 15%, 65%; 20%, 25%, 55%; 40%, 15%, 45%; and 40%, 25%, 35%, respectively. The following 2 diet categories were defined to test interactions with dietary fat: low fat (2 diets with the aim of 20% from total energy) and high fat (2 diets with the aim of 40% from total energy). Results showed that individuals with the TT genotype for rs12255372 had a greater decrease in BMI at 6 month follow-up visit than those who carried the C allele when subjects consumed a low-fat diet compared to a high-fat diet at the same time point. But the results disappeared after 6 months of intervention, which was likely because of diminished adherence to randomized dietary targets from 6 months to 2 years.
How dietary fats and genes modulate responses in weight and obesity remains unclear. In light of the available literature, it may be possible that all 3 macronutrients (total fat, protein, carbohydrate) modulate the effect of TCF7L2 gene through different pathways. However, the achievement of full compliance in dietary trials is difficult beyond 6-12 months, because it requires people to continue diet. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/23034957/
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