Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control
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.
From the paper
- Animals
Amino acids from C57BL/6J male and female 15 m old mice were analyzed at the Australian Proteome Analysis Facility, Macquarie University, using the Waters AccQ-Tag Ultra Chemistry Kit (Waters Corporation).
- Limitation
First, our experiments did not directly measure BCAA turnover and metabolism and therefore the fate of excess dietary BCAAs, and whether they contribute directly to adiposity, remain unclear.
Quoted word for word from the full text on PubMed Central.
The paper
The University of Sydney
Nature Metabolism, 29 Apr 2019, Open access, accepted manuscript
