Dominick J Lemas1,2, Yann C Klimentidis3, Stella Aslibekyan4, Howard W Wiener4, Diane M O'Brien1, Scarlett E Hopkins1, Kimber L Stanhope5,6, Peter J Havel5,6, David B Allison7,8,9, Jose R Fernandez8,10, Hemant K Tiwari7, Bert B Boyer1. 1. Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, USA. 2. Department of Pediatrics, Section of Neonatology, University of Colorado Denver, Aurora, CO, USA. 3. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA. 4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. 5. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. 6. Department of Nutrition, University of California, Davis, CA, USA. 7. Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. 8. Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. 9. Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, USA. 10. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract
SCOPE: n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. MATERIALS AND METHODS: Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. CONCLUSION: The results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people.
SCOPE: n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes. MATERIALS AND METHODS: Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels. CONCLUSION: The results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people.
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