Niacin: an old lipid drug in a new NAD+ dress

Mario Romani,Dina Carina Hofer,Elena Katsyuba,Johan Auwerx

doi:10.1194/jlr.s092007

Abstract

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated. In addition to its historically well-defined interactions with central players of lipid metabolism, niacin can be processed by eukaryotic cells to synthesize a crucial cofactor, NAD+ NAD+ acts as a cofactor in key cellular processes, including oxidative phosphorylation, glycolysis, and DNA repair. More recently, evidence has emerged that NAD+ also is an essential cosubstrate for the sirtuin family of protein deacylases and thereby has an impact on a wide range of cellular processes, most notably mitochondrial homeostasis, energy homeostasis, and lipid metabolism. NAD+ achieves these remarkable effects through sirtuin-mediated deacetylation of key transcriptional regulators, such as peroxisome proliferator-activated receptor gamma coactivator 1-α, LXR, and SREBPs, that control these cellular processes. Here, we present an alternative point of view to explain niacin's mechanism of action, with a strong focus on the importance of how this old drug acts as a control switch of NAD+/sirtuin-mediated control of metabolism.

Highlights

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins
Nicotinic acid was identified in the beginning of the 20th century by Conrad Elvehjem [1] as an effective treatment for pellagra, which at that time was endemic in the United States
The name of nicotinic acid was replaced by niacin in the 1940s to avoid any association with nicotine [2], and a decade later, the lipid-modulating effects of this molecule were described in patients by Rudolf Altschul [3], making niacin the oldest lipid-lowering drug

Summary

Introduction

The first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. NAD+ achieves these remarkable effects through sirtuin-mediated deacetylation of key transcriptional regulators, such as peroxisome proliferator-activated receptor gamma coactivator 1- , LXR, and SREBPs, that control these cellular processes. Despite the fact that several of the molecular mechanisms underlying its remarkable effects on lipid metabolism have been elucidated since the molecular mechanism of how niacin works remains elusive. Niacin acts as a broad-spectrum lipid-modulating drug and increases the circulating levels of HDL [4] (Fig. 1). This class of lipoproteins, which is enriched with ApoA-I and ApoA-II, are major players in reverse cholesterol transport. A. acts as a consultant to Mitobridge-Astellas and TES Pharma, which are developing NAD-boosting drugs

Objectives

Conclusion