Journal
CELL METABOLISM
Volume 34, Issue 2, Pages 209-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2021.12.018
Keywords
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Categories
Funding
- NIA [AG056771, AG062328, AG061635]
- NIDDK [DK125859]
- UW-Madison
- Dalio Philanthropies
- American Diabetes Association [1-17-PDF-076]
- Diabetes Research Center at Washington University [P30DK020579]
- UWBIRCWH Scholars Program award [K12HD101368]
- UWCCC support grant [P30 CA014520]
- Wisconsin Head and Neck Cancer SPORE CEP [P50DE026787]
- Wisconsin Alumni Research Foundation
- US Department of Veterans Affairs [I01-BX004031]
- William S. Middleton Memorial Veterans Hospital
- American Heart Association [17PRE33410983]
- Supplement to Promote Diversity in Health-Related Research [R01AG062328-03S1]
- [F31AG066311]
- [T32AG000213]
- [T32DK007665]
- [DP1DK113643]
- [P30DK019525]
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Research has found that the improvement of metabolic health through reduced dietary protein strongly depends on sex and strain. While some phenotypes remain consistent across different strains and sexes, there is high variability in adiposity, insulin sensitivity, and circulating hormones.
Low-protein diets promote metabolic health in humans and rodents. Despite evidence that sex and genetic background are key factors in the response to diet, most protein intake studies examine only a single strain and sex of mice. Using multiple strains and both sexes of mice, we find that improvements in metabolic health in response to reduced dietary protein strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, we observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, we identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, providing molecular insight into the differential response to protein restriction. Our results highlight the importance of sex and genetic background in the response to dietary protein level, and the potential importance of a personalized medicine approach to dietary interventions.
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