Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.
Obesity (Silver Spring). 2013 Mar;21(3):602-8. doi: 10.1002/oby.20001.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not been evaluated for obesity in people.
We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area.We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area.
In multivariable linear regression models, we dichotomized saturated fat intake and found significant interaction terms between total saturated fatty acids and LRP1 rs1799986 genotype for BMI (P=0.006) and hip (P = 0.002). High intake of saturated fat was associated with higher BMI (P = 0.001), waist (P = 0.008) and hip (P=0.003) in minor allele carriers (CT+TT) compared to CC participants. Further analysis of dichotomized individual saturated fatty acids revealed that interactions were strongest for two individual longer chain fatty acids. High intake of palmitic acid (C16:0; P = 0.0007) and high stearic acid intake (C18:0; P = 0.005) were associated with higher BMI in T carriers. Interactions were not detected for polyunsaturated fatty acids.
Gene-diet interactions at the LRP1 locus support the hypothesis that susceptibility to weight gain based on saturated fatty acids is modified by genotype and possibly by chain length. These results may facilitate the development of a panel of genetic candidates for use in optimizing dietary recommendations for obesity management.
载脂蛋白相关蛋白 1（LRP1）是一种多功能内吞受体，在脂肪细胞和下丘脑中有高表达。动物模型和体外研究支持 LRP1 在脂肪代谢和瘦素信号中的作用，但尚未对其遗传多态性与人类肥胖的关系进行评估。
我们研究了膳食脂肪（如饱和脂肪、多不饱和脂肪）是否调节了 LRP1 rs1799986 与人体测量特征的关联。我们研究了居住在波士顿地区的波多黎各人群（n=920，年龄 45-74 岁）的基于人群的样本。
在多元线性回归模型中，我们将饱和脂肪摄入量二分法，并发现总饱和脂肪酸与 LRP1 rs1799986 基因型之间存在显著的交互作用，用于 BMI（P=0.006）和髋部（P=0.002）。与 CC 参与者相比，在 CT+TT 携带者中，高饱和脂肪摄入量与 BMI（P=0.001）、腰围（P=0.008）和髋部（P=0.003）更高相关。对二分法的个体饱和脂肪酸的进一步分析表明，这些相互作用在两种个体长链脂肪酸中最强。棕榈酸（C16:0；P=0.0007）和硬脂酸（C18:0；P=0.005）摄入量高与 T 携带者的 BMI 更高相关。未检测到多不饱和脂肪酸的相互作用。
LRP1 基因座的基因-饮食相互作用支持了这样的假设，即基于饱和脂肪酸的体重增加易感性是由基因型和可能的链长修饰的。这些结果可能有助于开发一组遗传候选物，用于优化肥胖管理的饮食建议。
