Location: Obesity and Metabolism ResearchTitle: Improving metabolic health through precision dietetics in mice
|BARRINGTON, WILLIAM - Texas A&M University Health Science Center|
|WULFRIDGE, PHILLIP - Johns Hopkins University|
|GUNARATNA, RAMESH - Texas A&M University Health Science Center|
|ROJAS, CAROLINA - Texas A&M University Health Science Center|
|HOWE, SELENE - Texas A&M University Health Science Center|
|PERRY, AMIE - Texas A&M University Health Science Center|
|HUA, KUNJIE - University Of North Carolina|
|HANSEN, KASPER - Johns Hopkins University|
|FUCHS-YOUNG, ROBIN - Texas A&M University Health Science Center|
|POMP, DANIEL - University Of North Carolina|
|FEINBERG, ANDREW - Johns Hopkins University|
|THREADGILL, DAVID - Texas A&M University Health Science Center|
Submitted to: Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2017
Publication Date: 1/1/2018
Citation: Barrington, W.T., Wulfridge, P., Gunaratna, R.T., Rojas, C.M., Howe, S.Y., Perry, A., Hua, K., Hansen, K.D., Fuchs-Young, R., Bennett, B.J., Pomp, D., Feinberg, A.P., Threadgill, D.W. 2018. Improving metabolic health through precision dietetics in mice. Genetics. 208:399-417. https://doi.org/10.1534/genetics.117.300536.
Interpretive Summary: To test whether individuals may have optimal metabolic health on different diets as opposed to one diet based on a population response being healthiest for all individuals, we compared responses of four inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiltJ) to four diets for which extensive human epidemiological health outcome data is available (Western diet, traditional Mediterranean diet, traditional Japanese diet, ketogenic diet). In human populations, the high-fat, high-sugar Western diet is associated poor health outcomes, while the high-fat Mediterranean and low-fat Japanese diets are traditionally associated with healthy metabolic effects. The high-fat, low-carbohydrate ketogenic diet creates a unique metabolic state, which has proven to be beneficial for treatment of epilepsy and diabetes, and has gained popularity for weight loss In constructing these mouse diets, macronutrient ratios, fatty acid profiles, fiber content, and sources of ingredients were accurately matched to recapitulate the average human diet as closely as possible. Since all mice in an inbred strain are genetically identical, with genetic diversity among different inbred strains being comparable to that between unrelated people, this study is analogous to investigating diet responses of four unrelated people, but with the ability to test multiple diets simultaneously in genetically-identical replicates while controlling environmental factors. The results encourage an approach to nutrition studies that embraces individual differences rather than attempting to fit everyone to an average that is reflective of few individuals.
Technical Abstract: Epidemiological studies comparing dietary patterns of populations with health outcomes have historically provided the basis for healthy diet recommendations. However, health effects in individuals often do not match mean population responses. To determine whether individuals benefit from current recommendations based on population data, or are healthiest on diets matched to each individual’s genetics, phenotypes related to metabolic syndrome were monitored in four inbred mouse strains fed one of four diets previously studied epidemiologically in humans. When all strains were grouped, average responses of the population mirrored responses of human populations but were not representative of the response in any individual strain. Rather, susceptibility to negative dietary health effects was highly variable by strain, with evidence that some individuals are resilient to the effects of certain diets. Mechanisms underlying development of metabolic syndrome also varied by strain and diet, with evidence of strain-dependent metabolic advantage. Epigenetic analysis revealed Avpr1a as a biomarker for adverse health effects of the Western diet. Contrary to current dietary guidelines, calorie intake was largely not predictive of adiposity. These diverse genetic background-dependent dietary effects demonstrate the highly individual nature of diet response and underscore the need for precision dietetics rather than a one-size-fits-all approach to diet recommendations to optimize health of individuals.