Table 8

POSITIVE EFFECTS OF PPARalpha AND PPARgamma AGONISTS

    PPAR alpha: Lipid Effects

a). Primarily a VLDL-Cholesterol (triglyceride) by increasing lipoprotein lipase and secondary LDL-Cholesterol lowering.

b). HDL-cholesterol raising effect by increasing the expression of apo A-I and apo A-II. Positive outcomes of the Fibric acid (Gemfibrozil) (VA-HIT) and Fenofibrate (DAIS) studies.

    PPAR gamma effects:

a).

    Primary Clinical Action
: (Insulin Sensitizers). Improving insulin mediated glucose uptake.

b). Decrease thrombotic, inflammatory and oxidative changes that contribute to endothelial cell dysfunction.

c). Improve vascular reactivity.

d). Decrease plasminogen activator inhibitor-1 (PAI-1).

e). Decrease moncyte expression NFkappa-B.

f).

    Anti-inflammatory effects
: Inhibition of macrophage activation and the production of inflammatory cytokines (TNFalpha, interleukin 6 and 1beta).
    New findings
: May be through the effects of PPARdelta.

g). Decrease C-reactive protein and IL-6 (both markers of inflammation and cardiovascular risk). Dandonna P reference. Diabetes Technol Ther. 2002; 4(6): 809–15.

h). Inhibit vascular SMC migration and proliferation.

i). Lower blood pressure.

j). Attenuate myocardial hypertrophy and protect against ischemia-reperfuion injury.

k). Preserve pancreatic islet Beta cell function.

l).

    Attenuate (specifically rosiglitazone) oxidative and nitrative stress
: enhanced PPAR gamma expression, improved endothelium – dependent vasodilation, preserved P-VASP, suppressed gp91(phox) of the membranous NAD(P)H Oxidase enzyme, reduced superoxide and total NOx (stable metabolic byproducts of NO) production, and inhibited nitrotyrosine formation.

m).

    Increase levels of Adiponectin.


Hayden and Tyagi Nutrition Journal 2004 3:4   doi:10.1186/1475-2891-3-4

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