期刊
NUTRITION & DIABETES
卷 12, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41387-022-00200-8
关键词
-
资金
- German Research Foundation (DFG) [WE6488/1-1, 491394008]
This study investigates the roles of branched-chain amino acids (BCAA) in metabolic health and finds that leucine has beneficial effects on adiposity and insulin sensitivity, while valine intake worsens glucose tolerance and insulin sensitivity.
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.
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