title: Acrolein-induced dyslipidemia and acute-phase response are independent of HMG-CoA reductase.
abstract: METHODS
  Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure.
  
  
  RESULTS
  Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15  min. By 6  h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute-phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase.
  
  
  CONCLUSIONS
  Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function.
authors.affiliation: Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292, USA. dj.conklin@louisville.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: Russell A
authors.initials: RA
authors.lastname: Prough
authors.forename: Peter
authors.initials: P
authors.lastname: Juvan
authors.forename: Tadeja
authors.initials: T
authors.lastname: Rezen
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
authors.forename: Petra
authors.initials: P
authors.lastname: Haberzettl
authors.forename: Sanjay
authors.initials: S
authors.lastname: Srivastava
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000210:Acute-Phase Reaction / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D050171:Dyslipidemias / Q000139:chemically induced* / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000685:Serum Amyloid A Protein / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic; D014280:Triglycerides / Q000097:blood; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C506119:Insig1 protein, mouse; C506120:Insig2 protein, mouse; D008565:Membrane Proteins; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D015262:Xenobiotics; D000171:Acrolein; D002784:Cholesterol; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases