Although the function of the PPARdelta variant remains unknown, evidence coming from different rodent model systems indicates that the PPARalpha plays a crucial role in hepatic lipid metabolism, whereas PPARgamma participates in adipocyte differentiation and function. Due to the involvement of different PPAR variants, fibrates and thiazolidinediones act through distinct and complementary mechanisms on plasma triglyceride metabolism. The identification of the molecular mechanism of action of these pharmacological agents, and the role distinct transcription factors of the PPAR family play therein, suggests that compounds activating both PPARalpha and PPARgamma should be very potent hypotriglyceridemic drugs, which may be of use in the treatment of the dyslipidemia associated with atherosclerosis and non-insulin dependent diabetes mellitus. The Sequestration of Bile Acids, A Non-Absorbed Method for Cholesterol Reduction. W. Harry Mandeville and Dennis I. Goldberg.
Cholesterol lowering therapies are available which act via several different mechanisms.
The therapeutic classes currently available whic afford these mechanisms are diet, statins, fibrates, niacin, probucol and sequestrants. This review will focus on the various bile acid sequestrants, a class of therapeutics which has been underutilized due to patient compliance issues attributed to the quantity of material required for effective treatment. Reynold Homan and Brian R. Krause. The growing evidence linking elevated plasma cholesterol levels to increased risk of heart disease and the demonstration of a positive correlation between plasma levels of low density lipoprotein cholesterol and cholesterol absorption efficiency in humans have been a major impetus for efforts to develop cholesterol absorption inhibitors. The potential for such agents is already evident from the clinical experience with neomycin and beta-sitosterol which have yicldcd moderate success in the treatment of hypercholesterolemic patients.