title: Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles.
abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes encoding cyclooxygenase 2 (cox2) and 5-lipoxygenase (5 lox), the products of which are involved in the inflammatory response, transcriptions were significantly upregulated in NP and BPA fish, whereas they were unchanged in t-OP specimens. The present findings suggest that dietary xenobiotic contamination can give rise to metabolic disorders also in fish and highlight the potential for their vertical transfer through the trophic levels and ultimately to humans.
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, 60131 Ancona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Maradonna
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, 60131 Ancona, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Nozzi
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, 60131 Ancona, Italy; INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Santangeli
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova, 16132 Genova, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Traversi
authors.affiliation: INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy; Dipartimento di Chimica, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Napoli, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gallo
authors.affiliation: Dipartimento Ambiente e Salute, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fattore
authors.affiliation: INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy.
authors.forename: D G
authors.initials: DG
authors.lastname: Mita
authors.affiliation: INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy; Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova, 16132 Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mandich
authors.affiliation: Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, 60131 Ancona, Italy; INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma, Italy. Electronic address: o.carnevali@univpm.it.
authors.forename: O
authors.initials: O
authors.lastname: Carnevali
mesh_terms: D000818:Animals; D004032:Diet; D005234:Fatty Liver / Q000139:chemically induced; D029941:Fish Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D021541:Sea Bream / Q000378:metabolism / Q000502:physiology*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D029941:Fish Proteins; D014874:Water Pollutants, Chemical; D015262:Xenobiotics
keywords: Bisphenol A; Diet; Nonylphenol; Obesogenic; Octylphenol; Sea bream