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Branched‐Chain Amino Acid–Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice
Author(s) -
Tanaka Hiroaki,
Fukahori Suguru,
Baba Shinji,
Ueno Takato,
Sivakumar Ramadoss,
Yagi Minoru,
Asagiri Kimio,
Ishii Shinji,
Tanaka Yoshiaki
Publication year - 2016
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607114555160
Subject(s) - medicine , antioxidant , endocrinology , methionine , endoplasmic reticulum , chemistry , nonalcoholic steatohepatitis , triglyceride , steatohepatitis , insulin resistance , lipid peroxidation , biochemistry , amino acid , biology , fatty liver , insulin , nonalcoholic fatty liver disease , cholesterol , disease
Background: The aim of the present study was to elucidate whether the administration of antioxidant‐rich nutrients, including branched‐chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects. Methods: Seven‐week‐old male KKAy mice fed a methionine‐ and choline‐deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and 4‐hydroxy‐2′‐nonenal (4‐HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress–related signaling in liver specimens obtained from mice in each group. Results: The morphometric grades of all NASH‐related findings and the mean degree of 8‐OHdG immunolocalization in groups D–F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p‐elF in groups E and F and those of phosphatidyl‐inositol 3 kinase (PI3K85), p‐AcelCoA, and PERK in group F were similar to those noted in group A. Conclusions: The administration of a combination of antioxidant‐rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.