MECHANISM OF ATHEROGENIC LIPID RESPONSE TO W-3 FISH OILS

Project: Research project

Project Details

Description

Omega-3 fatty acids (n-3FA) may have a role both in primary and secondary
prevention of coronary artery disease (CAD). Their protective effects are
partially attributed their lipid lowering properties. n-3FA consistently
lower the plasma triglycerides (TG). However their effects on low (LDL)
and high density (HDL) lipoproteins are variable. We observed that in
some patients with type II diabetes mellitus (DM), n-3FA fail to improve
plasma LDL or HDL and even raise the plasma protein (apo) B, suggesting an
increase in the number of LDL particles. Our work in Zucker rats, an
insulin resistant obese and hypertriglyceridemic model, suggested that n-
3FA lower the TG by suppressing the hepatic lipogenic enzymes. Our work lead us to postulate that of n-3FA suppress hepatic lipogenic
enzymes. This causes a reduction in the TG in very low density
lipoproteins (VLDL) and an associated decrease in their particle size;
which , together with a concurrent increase in lipoprotein lipase (LPL)
activity, expedites the conversion of VlDL to LDL. However, any resultant
increase in plasma LDL is more likely to occur in subjects with an abnormal
pre-treatment lipid profile or an abnormal apoE phenotype. n-3FA also
replace the fatty acids (FA) in VLDL an d alter lipolytic properties. Type
II diabetics are more susceptible to the effects of n-3FA, since they have
increased VLDL production and some decrease in their LPL reserve. We plan to challenge these hypothesis in four groups of type II diabetics,
categorized on the basis of their plasma lipids (normal, types IIa, IIb,
IV/V hyperlipidemias). We shall measure the TG content, Fa composition and
particle size of VLDL, LPL activity and the rate of in vivo and in vitro
lipolysis of VLDL into LDL before, during and after 12 wks treatment with
n-3FA. The responses observed will be correlated with patients' pre-
treatment lipid profiles and lipid profiles and apoE phenotypes. The
results obtained in diabetics will be compared to those obtained in age,
sex and weight matched non-diabetic controls. Type II DM associated with a two to three-fold increase in CAD. The
unfavorable lipid response we have observed in some subjects is not limited
to n-3FA therapy but can occur in response to fibric acid derivatives,
insulin or weight loss. Our study should provide information which can
improve the clinical management of type II DM.
StatusFinished
Effective start/end date5/1/904/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $99,929.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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