Camps Stefan G J A, Verhoef Sanne P M, Bouwman Freek G, Mariman Edwin C M, Westerterp Klaas R
Maastricht University, Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), 6200, MD, Maastricht, the Netherlands; Clinical Nutrition Research Centre (CNRC), Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR) and National University Health System (NUHS), Centre for Translational Medicine, 14 Medical Drive #07-02, MD6 Building, Yong Loo Lin School of Medicine, Singapore 117599, Singapore.
Maastricht University, Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), 6200, MD, Maastricht, the Netherlands.
Gene. 2019;721S:100019. doi: 10.1016/j.gene.2019.100019. Epub 2019 May 18.
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).
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: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. 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.
The heterozygotic genotype of FTO 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 ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss.
Carrying the minor ADRB2 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 FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.
能量限制会引起静息能量消耗（REE）和身体活动的适应性变化；个体间的差异可能归因于遗传易感性。本研究旨在探讨体重减轻导致的REE和身体活动变化是否受候选单核苷酸多态性（SNP）的影响。
148名受试者（39名男性，109名女性），平均年龄±标准差：41±9岁；体重指数（BMI）：31.9±3.0kg/m²，遵循极低能量饮食8周。从六个候选基因中选择SNP：ADRB2、FTO、MC4R、PPARG2、PPARD和PPARGC1A。在饮食前后评估REE（通风罩法）和身体活动（三轴加速度计）。一般线性模型包括所有参数的性别、年龄和其他相关协变量。
与纯合主要基因型（1.50M计数/天；CI 1.40-1.59）相比，FTO的杂合基因型与更高的身体活动量（1.71M计数/天；CI 1.62-1.81）相关（P<0.001），而纯合风险等位基因基因型在基线时无差异（1.56M计数/天；CI 1.39-1.74）；此外，能量限制后观察到类似模式。携带ADRB2的纯合次要基因型与体重减轻后REE的更大降低（P<0.05）和更大的适应性产热（P<0.05）相关。
携带纯合的ADRB2次要等位基因与饮食诱导的能量消耗代谢适应性增强有关，提示脂质动员减少起核心作用。携带纯合的FTO风险等位基因与基线或体重减轻后的低身体活动无关。一个FTO风险等位基因的杂合携带者在体重减轻前后表现出更大的身体活动，这可能部分保护他们免受与FTO相关的更高肥胖风险。
