Acrolein consumption induces systemic dyslipidemia and lipoprotein modification.
Aldehydes such as acrolein are ubiquitous pollutants present in automobile exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of several food substances and are present in drinking water, irrigation canals, and effluents from manufacturing plants. Oral intake represents the most significant source of exposure to acrolein and related aldehydes. To study the effects of short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma lipoproteins were assessed. Changes in hepatic gene expression related to lipid metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes, cytokines or liver enzymes, but increased plasma cholesterol and triglycerides. Similar results were obtained with apoE-null mice. Plasma lipoproteins from acrolein-fed mice showed altered electrophoretic mobility on agarose gels. Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and triglycerides levels with little change in LDL or HDL. NMR analysis indicated shifts from small to large VLDL and from large to medium-small LDL with no change in the size of HDL particles. Increased plasma VLDL was associated with a significant decrease in post-heparin plasma hepatic lipase activity and a decrease in hepatic expression of hepatic lipase. These observations suggest that oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and thereby contribute to cardiovascular disease risk.
Conklin
Daniel J
DJ
Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202, USA. dj.conklin@louisville.edu
Barski
Oleg A
OA
Lesgards
Jean-Francois
JF
Juvan
Peter
P
Rezen
Tadeja
T
Rozman
Damjana
D
Prough
Russell A
RA
Vladykovskaya
Elena
E
Liu
SiQi
S
Srivastava
Sanjay
S
Bhatnagar
Aruni
A
D000171:Acrolein / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000139:chemically induced*; D005786:Gene Expression Regulation; D008049:Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001057:Apolipoproteins E; D008074:Lipoproteins; D000171:Acrolein; D008049:Lipase