| Literature DB >> 31656947 |
Samantha M Solon-Biet1,2, Victoria C Cogger1,3,4,5, Tamara Pulpitel1,3, Devin Wahl1,3,4, Ximonie Clark1,2, Elena Bagley1,6, Gabrielle C Gregoriou1,6, Alistair M Senior1,2, Qiao-Ping Wang1,2,7, Amanda E Brandon1,3, Ruth Perks1, John O'Sullivan1,8, Yen Chin Koay1,8, Kim Bell-Anderson1,2, Melkam Kebede1,2, Belinda Yau1,2, Clare Atkinson1,2, Gunbjorg Svineng9, Timothy Dodgson1,2, Jibran A Wali1,2, Matthew D W Piper10, Paula Juricic11, Linda Partridge11, Adam J Rose12, David Raubenheimer1,2, Gregory J Cooney1,3, David G Le Couteur1,3,4,5, Stephen J Simpson1,2.
Abstract
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan. These effects are not due to elevated BCAA per se or hepatic mTOR activation, but rather due to a shift in the relative quantity of dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and is associated with central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes need not be due to intrinsic toxicity but, rather, a consequence of hyperphagia driven by AA imbalance.Entities:
Keywords: Nutrition; aging; appetite; branched chain amino acids; dietary balance; dietary restriction; lifespan; metabolic health; obesity; serotonin
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Year: 2019 PMID： 31656947 PMCID： PMC6814438 DOI： 10.1038/s42255-019-0059-2
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812