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Improvement of vascular dysfunction and blood lipids of insulin-resistant rats by a marine oil-based phytosterol compound

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Lipids

Abstract

The syndrome that is characterized by obesity, insulin resistance, and hyperlipidemia is increasingly prevalent in all prosperous societies. It is now recognized as a major contributor to cardiovascular disease. Vascular dysfunction in the form of hypercontractility and impaired nitric oxide-mediated relaxation is a significant component of cardiovascular disease, predisposing to ischemic events. The JCR:LA-cp strain of rats exhibits all major aspects of the obesity/insulin resistance syndrome, including vascular dysfunction and ischemic lesions of the heart. Dietary lipid intake may have a marked effect on plasma lipid levels and, potentially, on vascular disease. We have investigated the effects of a novel preparation, ONC101 (a phytosterol esterified with fish oil), on plasma lipids and vascular function in the insulin-resistant JCR:LA-cp rat. Treatment of obese male rats with ONC101 from 8 to 12 wk of age resulted in no change in plasma lipid concentrations at 0.5 g/kg body weight. At the higher dose of 2.6 g/kg, plasma TG fell 50% (1.26 vs. 2.59 mmol/L, P<0.002) and cholesterol esters were significantly reduced (1.34 vs. 1.61 mmol/l, P<0.002). Food intake and body weights were unaffected by ONC101 treatment. At the low dose of 86 mg/kg, the hypercontractility of aortic rings in response to phenylephrine was normalized and the relaxant response to acetylcholine was significantly improved. The results indicate that ONC101 at high doses has significant hypolipidemic effects and, at very low doses, has beneficial effects on endothelial and vascular smooth muscle cell function.

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Abbreviations

ACh:

acetylcholine

l NAME:

N G-nitro-l-arginine methyl ester

NO:

nitric oxide

PE:

phenylephrine

VLDL:

very low density lipoprotein

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Author information

Authors and Affiliations

  1. Ocean Nutrition Canada Ltd., B3J 1S5, Halifax, Nova Scotia

    H. Stephen Ewart, Jaroslav Kralovec & Jeffrey L. C. Wright

  2. Department of Biochemistry, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    Peter J. Dolphin

  3. Department of Surgery, 275 Heritage Medical Research Centre, University of Alberta, T6G 2S2, Edmonton, Alberta, Canada

    James C. Russell & Sandra E. Kelly

Authors
  1. James C. Russell
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  2. H. Stephen Ewart
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  3. Sandra E. Kelly
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  4. Jaroslav Kralovec
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  5. Jeffrey L. C. Wright
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  6. Peter J. Dolphin
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Correspondence to James C. Russell.

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Deceased, June 22, 2001.

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Russell, J.C., Ewart, H.S., Kelly, S.E. et al. Improvement of vascular dysfunction and blood lipids of insulin-resistant rats by a marine oil-based phytosterol compound. Lipids 37, 147–152 (2002). https://doi.org/10.1007/s11745-002-0874-6

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  • DOI: https://doi.org/10.1007/s11745-002-0874-6

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