Purpose: Nonalcoholic fatty liver disease (NAFLD) is defined by excessive lipid accumulation in the liver and involves an ample spectrum of liver diseases, ranging from simple uncomplicated steatosis to cirrhosis and hepatocellular carcinoma. Accumulating evidence demonstrates that high fructose intake enhances NAFLD development and progression promoting inhibition of mitochondrial β-oxidation of long-chain fatty acids and oxidative damages. l-Carnitine (LC), involved in β-oxidation, has been used to reduce obesity caused by high-fat diet, which is beneficial to ameliorating fatty liver diseases. Moreover, in the recent years, various studies have established LC anti-oxidative proprieties. The objective of this study was to elucidate primarily the underlying anti-oxidative mechanisms of LC in an in vitro model of fructose-induced liver steatosis. Methods: Human hepatoma HepG2 cells were maintained in medium supplemented with LC (5 mM LC) with or without 5 mM fructose (F) for 48 h and 72 h. In control cells, LC or F was not added to medium. Fat deposition, anti-oxidative, and mitochondrial homeostasis were investigated. Results: LC supplementation decreased the intracellular lipid deposition enhancing AMPK activation. However, compound C (AMPK inhibitor-10 μM), significantly abolished LC benefits in F condition. Moreover, LC, increasing PGC1 α expression, ameliorates mitochondrial damage-F induced. Above all, LC reduced ROS production and simultaneously increased protein content of antioxidant factors, SOD2 and Nrf2. Conclusion: Our data seemed to show that LC attenuate fructose-mediated lipid accumulation through AMPK activation. Moreover, LC counteracts mitochondrial damages and reactive oxygen species production restoring antioxidant cellular machine. These findings provide new insights into LC role as an AMPK activator and anti-oxidative molecule in NAFLD.
L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers / A. Montesano, P. Senesi, F. Vacante, G. Mollica, S. Benedini, M. Mariotti, L. Luzi, I. Terruzzi. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - 43:4(2020 Apr), pp. 493-503.
|Titolo:||L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers|
TERRUZZI, ILEANA MARINA (Corresponding)
|Parole Chiave:||fructose; hepatic steatosis; l-Carnitine; lipid deposition; metabolic disease; oxidative stress|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
|Data di pubblicazione:||apr-2020|
|Data ahead of print / Data di stampa:||8-nov-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s40618-019-01134-2|
|Appare nelle tipologie:||01 - Articolo su periodico|
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