Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension
Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension
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DOI：
10.2337/db18-0708
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发表时间：
2019-01-01
期刊：
影响因子：
7.7
通讯作者：
Yaghootkar, Hanieh
中科院分区：
文献类型：
--
作者：
Ji, Yingjie;Yiorkas, Andrianos M.;Yaghootkar, Hanieh
最近的遗传学研究已经确定了与肥胖和 2 型糖尿病风险相反的影响相关的等位基因。我们的目的是识别更多这些变异，并检验这样的假设：这种有利的肥胖等位基因与较高的皮下脂肪和较低的异位脂肪相关。我们将 MRI 数据与体脂百分比 (%) 和代谢特征的全基因组关联研究结合起来。我们报告了 14 个等位基因，包括 7 个新鉴定的等位基因，它们与较高的肥胖率相关，但具有良好的代谢特征。与之前的研究一致，携带更有利的肥胖等位基因的个体具有较高的体脂百分比和较高的体重指数，但患 2 型糖尿病、心脏病和高血压的风险较低。这些人的皮下脂肪也较高，但肝脏脂肪较低，内脏与皮下脂肪组织的比率也较低。与较高身体脂肪百分比、较低肝脏脂肪和较低 2 型糖尿病风险相关的个体等位基因包括 PPARG、GRB14 和 IRS1 中的等位基因，而 ANKRD55 中的等位基因却与较高内脏脂肪但较低 2 型糖尿病风险相关。大多数已确定的有利肥胖等位基因与较高的皮下脂肪和较低的肝脏脂肪有关，这种机制与在代谢低风险库中储存过量甘油三酯的有益效果一致。
Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to- subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.