TY  - JOUR
A1  - Bishop, Christopher Allen
A1  - Schulze, Matthias Bernd
A1  - Klaus, Susanne
A1  - Weitkunat, Karolin
T1  - The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Dairy intake, as a source of branched-chain amino acids (BCAA), has been linked to a lower incidence of type-2-diabetes and increased circulating odd-chain fatty acids (OCFA). To understand this connection, we aimed to investigate differences in BCAA metabolism of leucine and valine, a possible source of OCFA, and their role in hepatic metabolism. Male mice were fed a high-fat diet supplemented with leucine and valine for 1 week and phenotypically characterized with a focus on lipid metabolism. Mouse primary hepatocytes were treated with the BCAA or a Ppar alpha activator WY-14643 to systematically examine direct hepatic effects and their mechanisms. Here, we show that only valine supplementation was able to increase hepatic and circulating OCFA levels via two pathways; a PPAR alpha-dependent induction of alpha-oxidation and an increased supply of propionyl-CoA for de novo lipogenesis. Meanwhile, we were able to confirm leucine-mediated effects on the inhibition of food intake and transport of fatty acids, as well as induction of S6 ribosomal protein phosphorylation. Taken together, these data illustrate differential roles of the BCAA in lipid metabolism and provide preliminary evidence that exclusively valine contributes to the endogenous formation of OCFA which is important for a better understanding of these metabolites in metabolic health.
KW  - fatty acid metabolism
KW  - leucine
KW  - liver
KW  - OCFA
KW  - valine
Y1  - 2020
U6  - https://doi.org/10.1096/fj.202000195R
SN  - 0892-6638
SN  - 1530-6860
VL  - 34
IS  - 7
SP  - 9727
EP  - 9739
PB  - Wiley
CY  - Hoboken
ER  -