title: Ethanol and fatty acids impair lipid homeostasis in an in vitro model of hepatic steatosis.
abstract: Excess ethanol consumption and fatty acid intake lead to a cumulative effect on liver steatosis through still unclear mechanisms. This study aimed to characterize the lipid homoeostasis alterations under the exposure of hepatocytes to ethanol alone or combined with fatty acids. FaO hepatoma cells were incubated in the absence (C) or in the presence of 100 mM ethanol (EtOH) or 0.35 mM oleate/palmitate (FFA) alone or in the combination (FFA/EtOH). Content of intra- and extra-cellular triglycerides (TAGs) and of lipid droplets (LDs), expression of lipogenic and lipolytic genes, and oxidative stress-related parameters were evaluated. Exposure to either FFAs or EtOH given separately led to steatosis which was augmented when they were combined. Our results show that FFA/EtOH: (i) increased the LD number, but reduced their size compared to separate treatments; (ii) up-regulated PPARγ and SREBP-1c and down-regulated sirtuin-1 (SIRT1); (iii) impaired FFA oxidation; (iv) did not change lipid secretion and oxidative stress. Our findings indicate that one of the major mechanisms of the metabolic interference between ethanol and fat excess is the impairment of FFA oxidation, in addition to lipogenic pathway stimulation. Interestingly, ethanol combined with FFAs led to a shift from macrovesicular to microvesicular steatosis that represents a more dangerous condition.
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy.
authors: Giulia
authors: G
authors: Vecchione
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy; INBB, Istituto Nazionale Biostrutture e Biosistemi, Roma, Italy.
authors: Elena
authors: E
authors: Grasselli
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy.
authors: Andrea D
authors: AD
authors: Compalati
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy.
authors: Milena
authors: M
authors: Ragazzoni
authors: DIMES, Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy.
authors: Katia
authors: K
authors: Cortese
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy.
authors: Gabriella
authors: G
authors: Gallo
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy.
authors: Adriana
authors: A
authors: Voci
authors: DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, University of Genova, Genova, Italy; INBB, Istituto Nazionale Biostrutture e Biosistemi, Roma, Italy. Electronic address: laura.vergani@unige.it.
authors: Laura
authors: L
authors: Vergani
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000431:Ethanol / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005234:Fatty Liver; D006706:Homeostasis; D050356:Lipid Metabolism / Q000187:drug effects*; D051381:Rats
chemical_list: D005227:Fatty Acids; D000431:Ethanol
keywords: Alcoholic fatty liver disease; Fatty acid oxidation; Lipid accumulation; Lipid metabolism; Oxidative stress; Rat hepatoma cells