Low-density lipoprotein receptor-related protein 1 variant interacts with saturated fatty acids in puerto ricansa

Authors

  • Caren E. Smith,

    1. Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
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  • Katherine L. Tucker,

    1. Department of Health Sciences, Northeastern University, Boston, Massachusetts, USA
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  • Yu-Chi Lee,

    1. Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
    2. Tufts University School of Nutrition, Boston, Massachusetts, USA
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  • Chao-Qiang Lai,

    1. Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
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  • Laurence D. Parnell,

    1. Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
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  • José M. Ordovás

    Corresponding author
    1. Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA
    2. Tufts University School of Nutrition, Boston, Massachusetts, USA
    • Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA

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  • a

    Disclosure: The authors declared no conflict of interest.

  • Funding agencies: Supported by the National Institutes of Health, National Institute on Aging, grant number 5P01AG023394-02 and NIH/NHLBI grant number HL54776 and NIH/NIDDK DK075030 and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service.

Abstract

Objective:

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.

Design and Methods:

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.

Results:

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.

Conclusions:

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.

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