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Nutr Res. 2013 Nov;33(11):932-41. doi: 10.1016/j.nutres.2013.08.001. Epub 2013 Sep 18.

Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

Author information

1
Veterans Administration Healthcare System, Long Beach, CA, USA.

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.

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

PMID:
24176233
DOI:
10.1016/j.nutres.2013.08.001
[Indexed for MEDLINE]

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