Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/60308 https://orcid.org/0000-0002-8676-5738 https://orcid.org/0000-0001-6909-4568 |
| _version_ | 1811073746876760064 |
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| author | Noguchi, Yasushi Nishikata, Natsumi Shikata, Nahoko Kimura, Yoshiko Aleman, Jose O. Young, Jamey D. Koyama, Naoto Kelleher, Joanne Keene Takahashi, Michio Stephanopoulos, Gregory |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Noguchi, Yasushi Nishikata, Natsumi Shikata, Nahoko Kimura, Yoshiko Aleman, Jose O. Young, Jamey D. Koyama, Naoto Kelleher, Joanne Keene Takahashi, Michio Stephanopoulos, Gregory |
| author_sort | Noguchi, Yasushi |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:37:56Z |
| format | Article |
| id | mit-1721.1/60308 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:37:56Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/603082022-09-30T15:49:18Z Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice Noguchi, Yasushi Nishikata, Natsumi Shikata, Nahoko Kimura, Yoshiko Aleman, Jose O. Young, Jamey D. Koyama, Naoto Kelleher, Joanne Keene Takahashi, Michio Stephanopoulos, Gregory Massachusetts Institute of Technology. Department of Chemical Engineering Stephanopoulos, Gregory Noguchi, Yasushi Aleman, Jose O. Young, Jamey D. Kelleher, Joanne Keene Stephanopoulos, Gregory 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. National Institutes of Health (U.S) (Bioengineering Research Partnership Grant DK58533) National Institutes of Health (U.S) (NIH Metabolomics Roadmap Initiative DK070291) National Institutes of Health (U.S) (DK072856) 2010-12-17T18:26:20Z 2010-12-17T18:26:20Z 2010-08 2010-07 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/60308 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 https://orcid.org/0000-0002-8676-5738 https://orcid.org/0000-0001-6909-4568 en_US http://dx.doi.org/10.1371/journal.pone.0012057 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Noguchi, Yasushi Nishikata, Natsumi Shikata, Nahoko Kimura, Yoshiko Aleman, Jose O. Young, Jamey D. Koyama, Naoto Kelleher, Joanne Keene Takahashi, Michio Stephanopoulos, Gregory Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title | Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title_full | Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title_fullStr | Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title_full_unstemmed | Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title_short | Ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| title_sort | ketogenic essential amino acids modulate lipid synthetic pathways and hepatic steatosis in mice |
| url | http://hdl.handle.net/1721.1/60308 https://orcid.org/0000-0002-8676-5738 https://orcid.org/0000-0001-6909-4568 |
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