Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 31, 2012
Publication Date: March 1, 2013
Citation: Smith, C.E., Tucker, K.L., Lee, Y., Lai, C., Parnell, L.D., Ordovas, J.M. 2013. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans. Obesity. 21:602-608. Interpretive Summary: Obesity is recognized as a multi-factorial condition, in which genetic and environmental factors contribute to weight gain. The list of genes reported to be related to obesity continues to expand, and in some cases is based on evidence from animal models. Studies from genetically altered mice and from cells grown in the laboratory suggest that a protein called low density lipoprotein receptor related protein 1 (LRP1) plays a role in the metabolism of fat cells and also in eating behavior. A single study recently provided evidence that this gene was also related to obesity in people. We aimed to investigate not only the direct relationship between genetic variants of LRP1 and obesity, but also how diet affected these relationships. In a population of older Puerto Ricans living in the Boston, MA area, we observed that saturated fat intake modified the relationship between an LRP1 variant and greater body size. Specifically, people with greater intake of saturated fat who also carried a specific LRP1 variant were more likely to have greater body mass index (BMI), and larger waist and hip circumferences. This relationship between fat consumption and the LRP1 variant is referred to as a “gene-diet interaction”, and is an example of how the combination of diet and an individual’s genetics may increase the risk of obesity. The long-term objective of gene-diet interaction studies is to more effectively prevent obesity through the development of tailored dietary recommendations that are based on the genetic background of the individual.
Technical Abstract: Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional 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 (e.g., saturated, polyunsaturated) modulated the association of LRP1 variants 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.