Precision Nutrition: Sex, Strain, and Diet Dependent Response to Carbohydrate Restriction in Mice

Abstract

The nutrition care process encompasses the provision of nutrition care among four domains: Assessment, Diagnosis, Intervention, and Monitoring & Evaluation. As a component of precision medicine, precision nutrition will build upon the nutrition care process by taking genetic background into consideration along with the typical information collected during Assessment. We searched for genetic variants underlying differences in the responses to American and ketogenic diets between C57BL/6J (B6) and FVB/NJ (FVB) mice. We used an F2 population derived from these strains to investigate the genetic origin of differential response to carbohydrate restriction. We identified three loci regulating fat mass gained during the feeding trial (Fmgq1, Fmgq2, and Fmgq3). The confidence interval for Fmgq1 overlaps with a locus regulating serum HDL cholesterol concentration (Hdlq1) that harbors Apoa2 and has previously been associated with serum HDL cholesterol concentration. Fmgq1 may influence fat gain through an intermediate change in serum cholesterol. We also identified candidate genes at Fmgq1 and Fmgq2 associated with male hormone secretion. Linkage analysis for microbial traits identified genotype specific loci regulating microbial abundances as well as genotype-by-diet interactions and genotype-by-sex interactions. Lastly, we used our model to implement precision nutrition by exposing B6 and FVB mice to an American diet prior to the introduction of a ketogenic dietary intervention and observed low plasticity of the B6 male obese phenotype. These results demonstrate how precision nutrition will be advanced through integration of genetic variation and sex in physiological responses to diets varied in carbohydrate composition.