Revised: December 27, 2011
Accepted: April 10, 2012
Published online: June 9, 2012
Nicotinic acid (NA) comprises the oldest hypolipidemic drug, in use since 1955. Despite its established broad spectrum effect on lipid profile and the associated reduction in cardiovascular morbidity and mortality, the mechanisms by which NA achieves its beneficial effects remain elusive. Regarding the NA-associated reduction in triglyceride and low density lipoprotein cholesterol levels, data are controversial. The prevailing view which suggested that NA inhibits lipolysis and decreases free fatty acid (FFA) release both via activation of adipose tissue G-protein receptor-109A (GPR109A) and via inhibition of hepatic triglyceride synthesis is currently debated by the observation that the initially decreased FFA levels rebound during long-term NA treatment even though the beneficial NA effects on lipid metabolism are preserved, while other mechanisms involving modulation of transcription and translation pathways are emerging. In addition, NA has been demonstrated to affect high density lipoprotein (HDL) particles remodeling in a number of ways, including reducing cholesterol ester transfer protein levels and activity, increasing apolipoprotein A-I levels, eliminating HDL hepatic uptake, increasing cholesterol efflux via ATP-binding cassette A1, inhibiting hepatic lipase, thereby overall increasing the plasma residence time of HDL and apoA-I with retention of cholesterol esters in HDL. Focus of this article is to present the mechanisms by which NA exerts its broad spectrum hypolipidemic actions.