Acetyl-l-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease |
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Authors: | Elango Kathirvel Kengathevy Morgan Samuel W French Timothy R Morgan |
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Institution: | 1. Veterans Administration Healthcare System, Long Beach, CA, USA;2. Department of Medicine, University of California-Irvine, Irvine, CA, USA;3. Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA;4. Department of Medicine, UCLA, Los Angeles, CA USA |
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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. |
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Keywords: | ALC acetyl-l-carnitine ALT alanine aminotransferase AST aspartate aminotransferase BSA bovine serum albumin CoA coenzyme A CPS-1 cabamoyl phosphate synthase 1 H& E hematoxylin and eosin HF high fat LA lipoic acid MDA malondialdehyde NAFLD nonalcoholic fatty liver disease NASH nonalcoholic steatohepatitis SF standard fat WAT white adipose tissue |
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