Genetic Background Shapes Phenotypic Response to Diet for Adiposity in the Collaborative Cross

Frontiers in Genetics

Fernando Pardo-Manuel de Villena¹  Brian J. Bennett²  Jody Albright⁴  Melissa VerHague⁴  Phoebe Yam⁵  Erik R. Gertz⁵ 

[1] Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States;Department of Nutrition, University of California, Davis, Davis, CA, United States;Integrative Genetics and Genomics Graduate Group, University of California, Davis, Davis, CA, United States;Nutrition Research Institute, University of North Carolina, Chapel Hill, NC, United States;Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, CA, United States;

关键词: collaborative cross;    diet;    nutrigenomics and nutrigenetics;    genetics;    obesity;   

DOI  :  10.3389/fgene.2020.615012

来源: DOAJ

【 摘 要 】

Defined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics, and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.

【 授权许可】

Unknown