title: Chronic exposure to low-dose arsenic modulates lipogenic gene expression in mice.
abstract: Arsenic, a ubiquitous environmental toxicant, can affect lipid metabolism through mechanisms that are not well understood. We studied the effect of arsenic on serum lipids, lipid-regulating genes, and transcriptional regulator sterol regulatory element binding protein 1c (SREBP-1c). C57BL/6 mice were administered 0 or 100 ppb sodium arsenite in drinking water for 5 weeks. Arsenic exposure was associated with decreased liver weight but no change in body weight. Serum triglycerides level fell in arsenic-exposed animals, but not in fed animals, after short-term fasting. Hepatic expression of SREBP-1c was reduced in arsenic-exposed fed animals, with a 16-fold change in reduction. Similar effects were seen for SREBP-1c in white adipose tissue. However, fasting resulted in dissociation of the expression of SREBP-1c and its targets, and SREBP-1c protein content could not be shown to correlate with its mRNA expression. We conclude that arsenic modulates hepatic expression of genes involved in lipid regulation through mechanisms that are independent of SREBP-1c expression.
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA, 02543, USA; Department of Pathology, Brown University, Providence, RI, 02912, USA; Department of Pediatrics, Division of Endocrinology and Metabolism, Rhode Island Hospital, Providence, RI, 02903, USA. adeola_adebayo@brown.edu.
authors.forename: Adeola O
authors.initials: AO
authors.lastname: Adebayo
authors.forename: Fokko
authors.initials: F
authors.lastname: Zandbergen
authors.forename: Courtney D
authors.initials: CD
authors.lastname: Kozul-Horvath
authors.forename: Philip A
authors.initials: PA
authors.lastname: Gruppuso
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Hamilton
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D017670:Sodium Compounds / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C017947:sodium arsenite; D001151:Arsenic
keywords: Arsenic; Lipid Metabolism; Liver; Sterol Regulating Element-Binding Protein 1c; White Adipose Tissue