Effects of GLA Precursors Added to Atherogenic Diet on Platelet Insulin Sensitivity, Plasminogen Activator Activity and Atherogenic Plaque Development in Rabbits

Abstract

Maintaining rabbits on a diet containing 2%Cholesterol (Ch) for 4–6 weeks usually promotes development of hypercholesterolemia, diminished plasma plasminogen activator activity(PPA) and atherosclerotic plaque formation. Also tissue insulin sensitivity and tissue delta‐6‐desatuase (D‐6‐D) levels needed to convert cis cis linoleic acid(LA) to gamma linoleic acid (GLA) are lowered. GLA is a precursor for the anti‐atherogenic prostaglandin, Prostacyclin (PGE2) production in normal tissues.In this study, three groups of 5 New Zealand strain male rabbits were fed AD (2% Ch, 6%Corn Oil, 92% Purina Rabbit Chow) for an 8 week period.. In Group I – the AD Control animals‐ the rabbits were fed AD alone. Group II rabbits were fed AD supplemented with 5% LA and in Group III, the animals received AD with 5% PRO added. In blood plasma assays for plasminogen activator activity (PAA), mean PAA values found in Group I AD Control animals was 11.7 %. In the (LA+ AD) Group II samples, it was 15.7% and 16.6% in (PRO+AD)‐Group III assays. The mean for blood cholesterol levels was 689.9mg% in the Group I AD Controls and lowered to 612.4 mg% in the (LA+AD) Group II and 595.1 mg% in the (PRO+AD) Group III samples. Tissue insulin sensitivity was measured by assaying blood platelet glucose content after incubation with exogenous glucose and insulin. Group I AD Control platelets had a mean value of 219.2 mg% Glucose. In (LA+AD) Group II, it increased to 304.4 mg% and in (PRO+AD) Group III‐ platelets, the mean was 308.7mg%. Gas chromatographic analyses of the aortae assayed for Linoleic Acid levels found a mean of 2645 nmol/mg dry wt. in Group I AD controls, 4310nmol/mg for LA+AD Group II aortae and 4290nmol/mg in the PRO+AD Group III aortae. Assays for GLA levels in aortae from AD Group I gave 10.1 nmol/mg dry wt., for LA+AD Group II, the value was 172nmol/gm and for PRO+AD Group III‐ it was 540nmol/mg.Atherosclerotic plaque present in the wall of the aortae, estimated on a scale of 0–5, indicated the maximum aortal plaque development was 4.5 in AD Control Group I rabbits, 3.5 in LA+AD Group II and 2.5 in P RO+AD Group III aortae.Addition of linoleic acid and primrose oil to AD, appeared to reduce atherogenesis that follows feeding rabbits AD alone. Addition of LA and PRO to AD increased blood levels of fibrinolytic activity and tissue sensitivity to insulin. These supplements lowered blood cholesterol and increased tissue levels of LA and GLA opposing the effects of AD dieting lacking them. Addition of LA and PRO to AD dieted rabbits resulted in increased tissue GLA levels which serve as a precursor for synthesis of the antiatherogenic Prostacylin (PGE2) in tissues.Support or Funding InformationFunded by a grant from the American Heart Association