How does nicotinic acid modify the lipid profile?
Dyslipidemia and Atherosclerosis Research Unit U 551 INSERM Hôpital de la Pitié 83, boulevard de l'Hôpital, 75651 Paris Cedex 13, France
Corresponding author. Tel: +33 1 42 17 78 78; fax: +33 1 42 17 78 78. E-mail address: chapman{at}chups.jussieu.fr
An atherogenic dyslipidaemic phenotype, characterized by low HDL-cholesterol levels, hypertriglyceridaemia and small, dense LDL, is commonly observed in patients with type 2 diabetes, the metabolic syndrome, or pre-existing cardiovascular disease and is inadequately addressed by current guidelines for the management of cardiovascular disease. Moreover, low HDL-cholesterol, in particular, is common among patients treated for dyslipidaemia and is little affected by statin treatment. Incomplete suppression of lipolysis by insulin in the fed state in insulin-resistant subjects leads to increased lipolysis in adipose tissue with elevated circulating free fatty acids (FFA). This metabolic abnormality leads directly to the development of the atherogenic dyslipidaemic phenotype. Nicotinic acid increases levels of HDL-cholesterol, probably largely through suppression of lipolysis in adipocytes secondary to activation of specific, G-protein-coupled nicotinic acid (HM74A) receptors. The reduction in FFA flux after nicotinic acid treatment also results in reduced levels of circulating triglycerides, mainly in the form of VLDL, and increased size and buoyancy of LDL. Treatment with nicotinic acid equally increases the size of HDL particles, which may promote increased reverse cholesterol transport from macrophages in the atherosclerotic plaque via the ABCG1 cholesterol transporter. The effects of nicotinic acid on the lipid profile are thus potentially anti-atherogenic and may address a major source of cardiovascular risk in insulin-resistant populations, such as those with the metabolic syndrome, type 2 diabetes and/or cardiovascular disease.
Key Words: HDL-cholesterol • Atherosclerosis • Dyslipidaemia • Nicotinic acid • Niacin • Lipolysis