Association of and gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

Background: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).

Methods: 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: , , , , and . REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters.

Results: The heterozygotic genotype of was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss.

Conclusion: Carrying the minor allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with .