Abstract
Background/objectivesThere is a growing appreciation for individual responses to diet. In a previous study, mouse strain-specific responses to American and ketogenic diets were observed. In this study, we searched for genetic variants underlying differences in the responses to American and ketogenic diets between C57BL/6J (B6) and FVB/NJ (FVB) mouse strains.ResultsGenetic mapping of fat and lean mass gain revealed QTLs on Chromosome (Chr) 1 at 191.6 Mb (Fmgq1) (P < 0.001, CI = 180.2–194.4 Mb), Chr5 at 73.7 Mb (Fmgq2, Lmgq1) (P < 0.001, CI = 66.1–76.6 Mb), and Chr7 at 40.5 Mb (Fmgq3) (P < 0.01, CI = 36.6–44.5 Mb). Analysis of serum HDL cholesterol concentration identified a significant (P < 0.001, CI = 160.6–176.1 Mb) QTL on Chr1 at 168.6 Mb (Hdlq1). Causal network inference suggests that HDL cholesterol and fat mass gain are both linked to Fmgq1.ConclusionsStrong sex effects were identified at both Fmgq2 and Lmgq1, which are also diet-dependent. Interestingly, Fmgq2 and Fmgq3 affect fat gain directly, while Fmgq1 influences fat gain directly and via an intermediate change in serum cholesterol. These results demonstrate how precision nutrition will be advanced through the integration of genetic variation and sex in physiological responses to diets varied in carbohydrate composition.
Highlights
Efforts to provide individualized dietary recommendations based on genetic markers have been underway for several years
The fat percentage of between C57BL/6J (B6) males consuming an American diet was 1.77-fold higher compared to B6 males consuming a ketogenic diet (B6 male American: 27.4 ± 5.2%, B6 male ketogenic: 15.5 ± 7.1%, P = 0.001, CI = 5.8–18.0%; Fig. 1 and Supplementary Table 3)
It is possible that the genetic architecture for fat gain in response to high-fat diets is more complex in females than in males, and as such, the genetic component we are able to detect in our model contributes more to the overall response in males than in females
Summary
We screened 6-week-old B6 and FVB mice for their response to American (35% of energy from fat, 50% from carbohydrates) and ketogenic (84% of energy from fat, 0% from carbohydrates) diets after a 6-month feeding trial. These strains have previously exhibited significantly different responses to these two diets [4]. Mice were randomly assigned to one of the two diet groups. At the end of the feeding trial, mice were euthanized by carbon dioxide asphyxiation, blood was collected, and tissues were harvested and immediately flash-frozen in liquid nitrogen
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