@article{4108,
  keywords = {Animals, Mice, Humans, Mice, Inbred C57BL, Male, Energy Metabolism, Mice, Knockout, Diet, Fibroblast Growth Factors, Amino Acids, Branched-Chain, Obesity, Mechanistic Target of Rapamycin Complex 1, Liver, Isoleucine, Valine, Adipose Tissue, White, Protein Serine-Threonine Kinases, Body Mass Index, Uncoupling Protein 1},
  author = {Deyang Yu and Nicole Richardson and Cara Green and Alexandra Spicer and Michaela Murphy and Victoria Flores and Cholsoon Jang and Ildiko Kasza and Maria Nikodemova and Matthew Wakai and Jay Tomasiewicz and Shany Yang and Blake Miller and Heidi Pak and Jacqueline Brinkman and Jennifer Rojas and William Quinn and Eunhae Cheng and Elizabeth Konon and Lexington Haider and Megan Finke and Michelle Sonsalla and Caroline Alexander and Joshua Rabinowitz and Joseph Baur and Kristen Malecki and Dudley Lamming},
  title = {The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.},
  abstract = { <p>Low-protein diets promote metabolic health in rodents and humans, and the benefits of low-protein diets are recapitulated by specifically reducing dietary levels of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we demonstrate that each BCAA has distinct metabolic effects. A low isoleucine diet reprograms liver and adipose metabolism, increasing hepatic insulin sensitivity and ketogenesis and increasing energy expenditure, activating the FGF21-UCP1 axis. Reducing valine induces similar but more modest metabolic effects, whereas these effects are absent with low leucine. Reducing isoleucine or valine rapidly restores metabolic health to diet-induced obese mice. Finally, we demonstrate that variation in dietary isoleucine levels helps explain body mass index differences in humans. Our results reveal isoleucine as a key regulator of metabolic health and the adverse metabolic response to dietary BCAAs and suggest reducing dietary isoleucine as a new approach to treating and preventing obesity and diabetes.</p> },
  year = {2021},
  journal = {Cell Metab},
  volume = {33},
  pages = {905-922.e6},
  month = {2021 May 04},
  issn = {1932-7420},
  doi = {10.1016/j.cmet.2021.03.025},
  language = {eng},
}