title: Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice.
abstract: Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2-3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.
authors: Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan. motoko.o@faculty.chiba-u.jp
authors: Motoko
authors: M
authors: Oarada
authors: Tsuyoshi
authors: T
authors: Tsuzuki
authors: Takeshi
authors: T
authors: Nikawa
authors: Shohei
authors: S
authors: Kohno
authors: Katsuya
authors: K
authors: Hirasaka
authors: Tohru
authors: T
authors: Gonoi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002364:Caseins / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D017781:Genes, Immediate-Early; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D009053:Sarcoma Viruses, Murine; D000637:Transaminases / Q000097:blood*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002364:Caseins; D004044:Dietary Proteins; D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D000637:Transaminases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase