Vaijinath S Kamanna1, Shobha H Ganji, Moti L Kashyap. 1. Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach, California 90822, USA. vaijinath.kamanna@va.gov
Abstract
PURPOSE OF REVIEW: This review focuses on the current understanding of the physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. RECENT FINDINGS: Emerging findings indicate that niacin decreases hepatic triglyceride synthesis and subsequent VLDL/LDL secretion by directly and noncompetitively inhibiting hepatocyte diacylglycerol acyltransferase 2. Recent studies in mice lacking niacin receptor GPR109A and human clinical trials with GPR109A agonists disproved the long believed hypothesis of adipocyte triglyceride lipolysis as the mechanism for niacin's effect on serum lipids. Niacin, through inhibiting hepatocyte surface expression of β-chain ATP synthase, inhibits the removal of HDL-apolipoprotein (apo) AI resulting in increased apoAI-containing HDL particles. Additional recent findings suggest that niacin by increasing hepatic ATP-binding cassette transporter A1-mediated apoAI lipidation increases HDL biogenesis, thus stabilizing circulation of newly secreted apoAI. New concepts have also emerged on lipid-independent actions of niacin on vascular endothelial oxidative and inflammatory events, myeloperoxidase release from neutrophils and its impact on HDL function, and GPR109A-mediated macrophage inflammatory events involved in atherosclerosis. SUMMARY: Recent advances have provided physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. Better understanding of niacin's actions on multiple tissues and targets may be helpful in designing combination therapy and new treatment strategies for atherosclerosis.
PURPOSE OF REVIEW: This review focuses on the current understanding of the physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. RECENT FINDINGS: Emerging findings indicate that niacin decreases hepatic triglyceride synthesis and subsequent VLDL/LDL secretion by directly and noncompetitively inhibiting hepatocyte diacylglycerol acyltransferase 2. Recent studies in mice lacking niacin receptor GPR109A and human clinical trials with GPR109A agonists disproved the long believed hypothesis of adipocyte triglyceride lipolysis as the mechanism for niacin's effect on serum lipids. Niacin, through inhibiting hepatocyte surface expression of β-chain ATP synthase, inhibits the removal of HDL-apolipoprotein (apo) AI resulting in increased apoAI-containing HDL particles. Additional recent findings suggest that niacin by increasing hepatic ATP-binding cassette transporter A1-mediated apoAI lipidation increases HDL biogenesis, thus stabilizing circulation of newly secreted apoAI. New concepts have also emerged on lipid-independent actions of niacin on vascular endothelial oxidative and inflammatory events, myeloperoxidase release from neutrophils and its impact on HDL function, and GPR109A-mediated macrophage inflammatory events involved in atherosclerosis. SUMMARY: Recent advances have provided physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. Better understanding of niacin's actions on multiple tissues and targets may be helpful in designing combination therapy and new treatment strategies for atherosclerosis.