TY  - JOUR
A1  - Bishop, Christopher Allen
A1  - Machate, Tina
A1  - Henning, Thorsten
A1  - Henkel-Oberländer, Janin
A1  - Püschel, Gerhard
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Klaus, Susanne
A1  - Weitkunat, Karolin
T1  - Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle
JF  - Nutrition & Diabetes
N2  - 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 (3HIB). 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.
Y1  - 2022
U6  - https://doi.org/10.1038/s41387-022-00200-8
SN  - 2044-4052
VL  - 12
IS  - 1
PB  - Nature Publishing Group
CY  - London
ER  -