title: AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats.
abstract: BACKGROUND
  Previous work with metformin has shown that this antidiabetic agent improves nonalcoholic fatty liver in ob/ob mice. AMP-activated protein kinase (AMPK) is one of the major cellular regulators of lipid and glucose metabolism, and reportedly mediates the beneficial metabolic effects of metformin. In this study, we examined the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an AMPK activator, on an experimental model of ethanol-induced hepatic steatosis.
  
  
  METHODS
  Rats were randomly divided into three groups: (A) rats fed ethanol-containing liquid diet for six weeks; (B) rats pair-fed ethanol-containing liquid diet for six weeks, during the last three weeks of which they were subcutaneously injected with 0.5 mg AICAR/g body weight per day; (C) rats pair-fed isocaloric liquid diet without ethanol for six weeks. At the end of the six-week period, the animals were sacrificed. Serum and liver specimens were analyzed using biochemical and histologic methods, as well as real-time PCR.
  
  
  RESULTS
  Chronic ethanol feeding resulted in fatty liver both histologically and biochemically, whereas AICAR administration attenuated the degree of change in the liver. AICAR also decreased the hepatic sterol regulatory factor binding protein-1c (SREBP-1c) and reduced fatty acid synthase (FAS) expression; these changes led to reduced triglyceride synthesis in rat livers. Furthermore, detection of 4-hydroxy-2-nonenal (4-HNE)-protein adducts showed that the AICAR treatment also decreased the products of lipid peroxidation.
  
  
  CONCLUSIONS
  In this preclinical rat model, AICAR, an AMPK activator, appears to protect the liver from fatty changes associated with chronic alcohol use. As such, AICAR may have a role in the treatment and prevention of alcohol-induced fatty liver.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ando
authors.forename: Naoto
authors.initials: N
authors.lastname: Kitamura
authors.forename: Haruna
authors.initials: H
authors.lastname: Koizumi
authors.forename: Shinzo
authors.initials: S
authors.lastname: Kato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Horie
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kaneko
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Azuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagata
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D055372:AMP-Activated Protein Kinases; D000447:Aldehydes / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002492:Central Nervous System Depressants; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D020536:Enzyme Activators / Q000627:therapeutic use*; D000431:Ethanol; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000627:therapeutic use*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000447:Aldehydes; D002492:Central Nervous System Depressants; D015853:Cysteine Proteinase Inhibitors; D020536:Enzyme Activators; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D000620:Aminoimidazole Carboxamide; D000431:Ethanol; D064429:Fatty Acid Synthases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C027576:4-hydroxy-2-nonenal