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Decreased consumption of specific macronutrients promotes metabolic health and longevity
Author(s) -
Cummings Nicole Elise,
Radcliff Abigail,
Brodbeck Allison,
Ko Elizabeth,
Wu Jessica,
Sherman Dawn,
Williams Elizabeth,
Apelo Sebastian Arriola,
Barnes Macy,
Hacker Timothy,
Lamming Dudley
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.645.24
Subject(s) - calorie restriction , glycemic , longevity , calorie , valine , biology , endocrinology , amino acid , mtorc1 , fgf21 , population , leucine , medicine , metabolism , obesity , type 2 diabetes , diabetes mellitus , biochemistry , fibroblast growth factor , genetics , protein kinase b , apoptosis , receptor , environmental health
Calorie restriction (CR) is the nutritional ‘gold standard’ in lifespan extension, improving metabolic health in many metabolic organisms. This intervention is extremely difficult to sustain, especially in a population struggling with both obesity and readily available food sources. While CR limits the intake of all macronutrients, it's unclear what macronutrient drives these benefits. An attractive alternative to restricting all calories is to limit only certain macronutrients, changing the ratio of macronutrient intake. A low protein, high carbohydrate diet can increase lifespan and improve metabolic health in both rodents and humans. However, the specific amino acid composition of protein intake may have more of an impact on metabolism and aging than researchers and physicians previously thought. Our lab has previously determined that a diet restricted in branched chain amino acids (BCAAs; leucine, isoleucine, and valine) improves glycemic control and metabolic health in young, wild‐type mice. In addition, we have determined that reduced consumption of BCAAs does not induce the production of fibroblast growth factor 21 (FGF21), a hormone produced in fasting and protein restriciton, but does result in specific inhibition of the mechanistic Target of Rapamycin Complex 1 (mTORC1). We have since expanded our research to explore the effects of BCAA restriction in aged and metabolically disadvantaged mice. We find that Low BCAA diets rapidly reverse diet induced obesity, improving glucoregulatory control and inducing weight loss. When BCAAs or total protein are restricted in a progeroid mouse, we promote longevity and rescue some aspects of cardiac function. BCAA restriction improves weight and glycemic control of aged, wild‐type mice. Our results suggest that a reduction in dietary BCAAs promotes metabolic health and longevity, and may represent a highly translatable option to treat age‐related disease. Support or Funding Information The Lamming lab is supported by a K99/R00 Pathway to Independence Award to D.W.L. from the National Institute of Health/National Institute on Aging (AG041765), a New Investigator Program Award from the Wisconsin Partnership Program, and an Innovator Award from the Progeria Research Foundation, as well as startup funds from the UW‐Madison School of Medicine and Public Health and the UW‐Madison Department of Medicine. N.E.C. is supported in part by a training grant from the UW Institute on Aging (NIA T32 AG000213). This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government.