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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.
AuthorsAdeola O Adebayo, Fokko Zandbergen, Courtney D Kozul-Horvath, Philip A Gruppuso, Joshua W Hamilton
JournalJournal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 29 Issue 1 Pg. 1-9 (Jan 2015) ISSN: 1099-0461 [Electronic] United States
PMID25155036 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2014 Wiley Periodicals, Inc.
Chemical References
  • Arsenites
  • Enzyme Inhibitors
  • Sodium Compounds
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • sodium arsenite
  • Arsenic
Topics
  • Adipose Tissue, White (metabolism)
  • Animals
  • Arsenic (pharmacology)
  • Arsenites (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Gene Expression Regulation (drug effects)
  • Lipogenesis (drug effects)
  • Liver (metabolism)
  • Male
  • Mice
  • Sodium Compounds (pharmacology)
  • Sterol Regulatory Element Binding Protein 1 (biosynthesis)
  • Triglycerides (biosynthesis)

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