title: Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation.
abstract: Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFkβ pathway (IκBα) by TNF-α was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-α blockage by anti-TNF-α in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-α).
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Gesa
authors.initials: G
authors.lastname: Martius
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Salamah Mohammad
authors.initials: SM
authors.lastname: Alwahsh
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fränk
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen D-37075 Goettingen, Germany ; Current address: Department of Radiation Oncology, Medizinische Hochschule Hannover Carl-Neuberg-Straße, 30625 Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen D-37075 Goettingen, Germany.
authors.forename: Ihtzaz Ahmed
authors.initials: IA
authors.lastname: Malik
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D050356:Lipid Metabolism / Q000528:radiation effects*; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
chemical_list: D018955:CD36 Antigens
keywords: FAT/CD36; Liver; cytokines; fat accumulation; inflammation; radiation