Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice
Name
Noguchi-2010-Ketogenic essential.pdf
Size
1.39 MB
Format
Adobe PDF
Checksum (MD5)
31f112ada4c03a8b2ae098c64a75dec8
Author(s)
Noguchi, Yasushi
Nishikata, Natsumi
Shikata, Nahoko
Kimura, Yoshiko
Aleman, Jose O.
Young, Jamey D.
Koyama, Naoto
Kelleher, Joanne Keene
Takahashi, Michio
Stephanopoulos, Gregory
Date Issued
August 2010
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Noguchi Y, Nishikata N, Shikata N, Kimura Y, Aleman JO, et al. (2010) Ketogenic Essential Amino Acids Modulate Lipid Synthetic Pathways and Prevent Hepatic Steatosis in Mice. PLoS ONE 5(8): e12057. doi:10.1371/journal.pone.0012057
Version
Final published version
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 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.
Conclusion
Our results indicate that dietary KAA intake improves hepatic steatosis and insulin resistance by modulating lipid synthetic pathways.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pone.0012057
