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Manipulation of Dietary Essential Amino Acids Prevents High‐Fat Induced Non‐Alcoholic Fatty Liver in Mice
Author(s) -
Noguchi Yasushi,
Hara Yoshiko,
Shikata Nahoko,
Aleman Jose O.,
Young Jamey D.,
Yoshida Shintaro,
Mori Masato,
Kelleher Joanne K.,
Takahashi Michio,
Stephanopoulos Gregory
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.614.17
Subject(s) - medicine , lipogenesis , endocrinology , postprandial , steatosis , hyperinsulinemia , chemistry , amino acid , triglyceride , glucokinase , cholesterol , lipid metabolism , biology , insulin resistance , insulin , biochemistry
We examined the effect of dietary essential amino acids (EAA) on high fat‐induced fat accumulation and hepatic steatosis in C57BL6 mice fed a high‐fat diet (HFD) which normally leads to obesity, hyperlipidemia and hyperinsulinemia. We designed a novel EAA supplemented high‐fat diet (HFED) in which dietary amino acids in the high‐fat diet, were partially replaced by EAA mixtures increasing the amounts of Lys, Thr, Leu, Ile and Val, without altering dietary protein‐amino acid (19%) or fat (52%) content. Mice were fed either HFD or HFED for 2 months. Results: Caloric intake was not different for the two diets, yet a significant reduction of fat mass, postprandial insulin, leptin and cholesterol occurred in HFED. Moreover, for HFED mice, hepatic triglyceride and cholesterol were greatly reduced, and plasma lipoproteins were normalized. The underlying mechanism was investigated measuring gene expression and metabolic flux at 8 weeks. HFED reduced hepatic gene expression for SREBP‐1c and its downstream genes including glucokinase and lipogenic genes. Metabolic flux analysis using deuterated water indicated that HFED repressed both de novo lipogenesis and desaturase flux compared to HFD. In summary, this study demonstrates that EAA supplementation prevents high‐fat induced hepatic steatosis and supports a mechanism by which EAA supplementation suppresses lipogenesis.