title: Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.
abstract: Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Clinical and Experimental Sciences, University of Brescia Medical School, 25121 Brescia, Italy; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy. Electronic address: lfontana@dom.wustl.edu.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Cummings
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
authors.forename: Sebastian I
authors.initials: SI
authors.lastname: Arriola Apelo
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Neuman
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Kasza
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Schmidt
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Edda
authors.initials: E
authors.lastname: Cava
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Medicine, University of Verona, 37129 Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spelta
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Medicine, University of Verona, 37129 Verona, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tosti
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
authors.forename: Faizan A
authors.initials: FA
authors.lastname: Syed
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Baar
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Geriatrics, Department of Medicine, University of Padova, 35122 Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Rural and Urban Scholars in Community Health Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cottrell
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Fenske
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bertozzi
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
authors.forename: Harpreet K
authors.initials: HK
authors.lastname: Brar
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Pietka
authors.affiliation: Division of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Arnold D
authors.initials: AD
authors.lastname: Bullock
authors.affiliation: Division of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Figenshau
authors.affiliation: Division of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Merrins
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Alexander
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kimple
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Rural and Urban Scholars in Community Health Program, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dlamming@medicine.wisc.edu.
authors.forename: Dudley W
authors.initials: DW
authors.lastname: Lamming
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose; D004044:Dietary Proteins / Q000008:administration & dosage; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005943:Gluconeogenesis; D018149:Glucose Intolerance; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000178:diet therapy*; D009929:Organ Size; D013312:Stress, Physiological
chemical_list: D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D004044:Dietary Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors