Dataset Information

Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.

ABSTRACT:

Background

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 lipogenesis (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.

Conclusion

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

SUBMITTER: Noguchi Y

PROVIDER: S-EPMC2919399 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Publications

Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.

Noguchi Yasushi Y Nishikata Natsumi N Shikata Nahoko N Kimura Yoshiko Y Aleman Jose O JO Young Jamey D JD Koyama Naoto N Kelleher Joanne K JK Takahashi Michio M Stephanopoulos Gregory G

PloS one 20100810 8

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 ...[more]

PMID: 20706589

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Dataset Information

Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.

Background

Methodology/principal findings

Conclusion

Publications

Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice.

Similar Datasets

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