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Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle

Title data

Bishop, Christopher A. ; Machate, Tina ; Henning, Thorsten ; Henkel, Janin ; Püschel, Gerhard ; Weber, Daniela ; Grune, Tilman ; Klaus, Susanne ; Weitkunat, Karolin:
Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle.
In: Nutrition & Diabetes. Vol. 12 (2022) . - 20.
ISSN 2044-4052
DOI: https://doi.org/10.1038/s41387-022-00200-8

Abstract in another language

OBJECTIVE: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake.
METHODS: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes).
RESULTS: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure—likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/
insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3-HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling.
CONCLUSION: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable
pathways in the etiology of BCAA-induced obesity and insulin resistance.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung
Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung > Lehrstuhl Biochemie der Ernährung - Univ.-Prof. Dr. Janin Henkel-Oberländer
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Date Deposited: 18 Sep 2023 08:34
Last Modified: 18 Sep 2023 08:34
URI: https://eref.uni-bayreuth.de/id/eprint/86873