title: Branched-Chain Amino Acid-Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan s_fukahori@med.kurume-u.ac.jp.
authors.forename: Suguru
authors.initials: S
authors.lastname: Fukahori
authors.affiliation: Asakura Medical Association Hospital, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Baba
authors.affiliation: Asakura Medical Association Hospital, Fukuoka, Japan Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ramadoss
authors.initials: R
authors.lastname: Sivakumar
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Asagiri
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Pediatric Surgery, Kurume University School of Medicine, Kurume, Japan Division of Medical Safety Management, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000032:analysis; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002794:Choline / Q000008:administration & dosage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004032:Diet; D019587:Dietary Supplements; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D051379:Mice; D018977:Micronutrients / Q000008:administration & dosage; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011972:Receptor, Insulin / Q000032:analysis; D014815:Vitamins
chemical_list: D000447:Aldehydes; D000597:Amino Acids, Branched-Chain; D000975:Antioxidants; D018977:Micronutrients; D014815:Vitamins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008715:Methionine; D011972:Receptor, Insulin; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D002794:Choline
keywords: antioxidant-rich nutrient; branched-chain amino acids; micronutrients; nonalcoholic steatohepatitis; selenium; vitamins; zinc