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Improving Metabolic Health Through Diets Depends on Genetic Background

The struggle to find the best diet for weight management and metabolic health improvement has largely failed. This failure may imply that no diet fits all needs, which justifies a search for biomarkers that can predict success in weight loss and physiological response, and can allow the most efficient diet to be selected on an individual basis. Researchers from the Texas A&M University recently conducted a series of metabolic studies to understand how genetic differences in mice influence health responses to several diets which are similar to those eaten by humans1.

The researchers designed four human-comparable mouse diets:

  • American-style diet: higher in fat and refined carbs, especially corn
  • Mediterranean diet: with wheat and red wine extract
  • Japanese diet: with rice and green tea extract
  • Ketogenic diet: high in fat with very few carbs

They compared the American diet’s impact on metabolic health, the liver metabolomic and epigenetic alterations associated with diet response to three healthier diets across four genetically distinct inbred mouse strains over a six-month period. American diet caused negative health effects across strains; however, severity of the effects on blood lipid profiles, glucose homeostasis, and liver triglycerides varied across genetic backgrounds. Diet-induced changes in liver metabolite levels were strain-dependent, with 84% of metabolites significantly altered by the American diet in only a single strain.

Next, they showed while each strain had a diet or diets that improved health relative to the American diet, no single diet improved health across all genetic background.  For example, a ketogenic diet improved glucose homeostasis and general health (metabolic rate and body composition) in two strains, while no benefits were observed in the other two strains. Beneficial impacts of the ketogenic diet on cholesterol profiles with decreased LDL cholesterol were observed across strains. The Japanese diet improved body composition across strains; however, did not consistently improve lipid profiles.  Also, a Japanese diet provided the greatest improvement in glucose metabolism of all diets for two strains. The Mediterranean diet did not improve body composition, but was beneficial for liver health in two strains and glucose metabolism in other strains.

Why is this Clinically Relevant?

  • In animal models, genetic variation may underlie the heterogeneity of diet response
  • This raise the question whether the development and implementation of personalized diet recommendations based on an individual’s genetic background could also lead to better outcomes in people
  • Additional factors such as the gut microbiome and individual-specific epigenetic differences may also play roles in diet response

Link to abstract


  1. Barrington W.T. et al. Improving metabolic health through precision dietetics in mice. Genetics 2017; 4:207

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