Ketogenic Essential Amino Acids Modulate Lipid Synthetic Pathways and Prevent Hepatic Steatosis in MiceReportar como inadecuado

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Although dietary ketogenic essential amino acid KAA content modifies accumulation of hepatic lipids, the molecular interactions between KAAs and lipid metabolism are yet to be fully elucidated.

Methodology-Principal Findings

We designed a diet with a high ratio E-N of essential amino acids EAAs to non-EAAs by partially replacing dietary protein with 5 major free KAAs Leu, Ile, Val, Lys and Thr without altering carbohydrate and fat content. This high-KAA diet was assessed for its preventive effects on diet-induced hepatic steatosis and whole-animal insulin resistance. C57B6 mice were fed with a high-fat diet, and hyperinsulinemic ob-ob mice were fed with a high-fat or high-sucrose diet. The high-KAA diet improved hepatic steatosis with decreased de novo lipogensis DNL fluxes as well as reduced expressions of lipogenic genes. In C57B6 mice, the high-KAA diet lowered postprandial insulin secretion and improved glucose tolerance, in association with restored expression of muscle insulin signaling proteins repressed by the high-fat diet. Lipotoxic metabolites and their synthetic fluxes were also evaluated with reference to insulin resistance. The high-KAA diet lowered muscle and liver ceramides, both by reducing dietary lipid incorporation into muscular ceramides and preventing incorporation of DNL-derived fatty acids into hepatic ceramides.


Our results indicate that dietary KAA intake improves hepatic steatosis and insulin resistance by modulating lipid synthetic pathways.

Autor: Yasushi Noguchi , Natsumi Nishikata , Nahoko Shikata , Yoshiko Kimura, Jose O. Aleman, Jamey D. Young, Naoto Koyama, Joanne K. Ke



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