Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control

Samantha M. Solon-Biet, Victoria C. Cogger, Tamara Pulpitel, Devin Wahl, Ximonie Clark, Gabrielle C. Gregoriou, Alistair M. Senior, Qiao-Ping Wang, Amanda E. Brandon, Ruth Perks, John O’Sullivan, Yen Chin Koay, Kim Bell-Anderson, Melkam Kebede, Belinda Yau, Clare Atkinson, Gunbjorg Svineng, Tim Dodgson, Jibran A. Wali, Matthew D. W. PiperPaula Juricic, Linda Partridge, Adam J. Rose, David Raubenheimer, Gregory J. Cooney, David G. Le Couteur, Stephen J. Simpson

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207 Citations (Scopus)


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 mammalian target of rapamycin activation, but instead are due to a shift in the relative quantity of dietary BCAAs and other amino acids, notably tryptophan and threonine. Increasing the ratio of BCAAs to these amino acids results 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 instead are a consequence of hyperphagia driven by amino acid imbalance.

Original languageEnglish
Pages (from-to)532-545
Number of pages14
JournalNature Metabolism
Issue number5
Publication statusPublished - 1 May 2019


  • ageing
  • feeding behaviour
  • metabolic diseases
  • nutrition

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