title: Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.
abstract: Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation.
authors.affiliation: Veterans Administration Healthcare System, Long Beach, CA, USA.
authors.forename: Elango
authors.initials: E
authors.lastname: Kathirvel
authors.forename: Kengathevy
authors.initials: K
authors.lastname: Morgan
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology / Q000627:therapeutic use*; D000273:Adipose Tissue / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D065626:Non-alcoholic Fatty Liver Disease; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D000108:Acetylcarnitine; D008063:Thioctic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: ALC; ALT; AST; Acetyl-L-carnitine; BSA; CPS-1; CoA; H&E; HF; High fat diet; LA; Lipoic acid; MDA; Mitochondria; Mouse; NAFLD; NASH; Nonalcoholic fatty liver; Oxidative stress; SF; WAT; acetyl-l-carnitine; alanine aminotransferase; aspartate aminotransferase; bovine serum albumin; cabamoyl phosphate synthase 1; coenzyme A; hematoxylin and eosin; high fat; lipoic acid; malondialdehyde; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; standard fat; white adipose tissue