Editing Niacin (section)

===Mechanisms===
Niacin reduces synthesis of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), [[lipoprotein(a)]] and [[triglycerides]], and increases [[high-density lipoprotein]] cholesterol (HDL-C).<ref name="Villines, T. C. 2012 p 14">{{cite journal | vauthors = Villines TC, Kim AS, Gore RS, Taylor AJ | s2cid = 27925461 | title = Niacin: the evidence, clinical use, and future directions | journal = Current Atherosclerosis Reports | volume = 14 | issue = 1 | pages = 49–59 | date = February 2012 | pmid = 22037771 | doi = 10.1007/s11883-011-0212-1 }}</ref> The lipid-therapeutic effects of niacin are partly mediated through the activation of [[G protein-coupled receptor]]s, including [[hydroxycarboxylic acid receptor 2]] (HCA<sub>2</sub>)and [[hydroxycarboxylic acid receptor 3]] (HCA<sub>3</sub>), which are highly expressed in [[adipose tissue|body fat]].<ref>{{cite journal | vauthors = Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K |title = Molecular identification of nicotinic acid receptor | journal = Biochemical and Biophysical Research Communications | volume = 303 | issue = 1 | pages = 364–9 | date = March 2003 | pmid = 12646212 | doi = 10.1016/S0006-291X(03)00342-5 }}</ref><ref>{{cite journal | vauthors = Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB | title = Molecular identification of high and low affinity receptors for nicotinic acid | journal = The Journal of Biological Chemistry | volume = 278 | issue = 11 | pages = 9869–74 | date = March 2003 | pmid = 12522134 | doi = 10.1074/jbc.M210695200 | doi-access = free }}</ref> HCA<sub>2</sub> and HCA<sub>3</sub> inhibit [[cyclic adenosine monophosphate]] (cAMP) production and thus suppress the release of free [[fatty acids]] (FFAs) from body fat, reducing their availability to the liver to synthesize the blood-circulating lipids in question.<ref name="Gille, A. 2008">{{cite journal | vauthors = Gille A, Bodor ET, Ahmed K, Offermanns S | title = Nicotinic acid: pharmacological effects and mechanisms of action | journal = Annual Review of Pharmacology and Toxicology | volume = 48 | issue = 1 | pages = 79–106 | year = 2008 | pmid = 17705685 | doi = 10.1146/annurev.pharmtox.48.113006.094746 }}</ref><ref>{{cite journal | vauthors = Wanders D, Judd RL | title = Future of GPR109A agonists in the treatment of dyslipidaemia | journal = Diabetes, Obesity & Metabolism | volume = 13 | issue = 8 | pages = 685–91 | date = August 2011 | pmid = 21418500 | doi = 10.1111/j.1463-1326.2011.01400.x | s2cid = 205536280 }}</ref><ref name=Costet2010>{{cite journal |vauthors=Costet P |title=Molecular pathways and agents for lowering LDL-cholesterol in addition to statins |journal=Pharmacol Ther |volume=126 |issue=3 |pages=263–78 |date=June 2010 |pmid=20227438 |doi=10.1016/j.pharmthera.2010.02.006 }}</ref> A decrease in free fatty acids also suppresses liver expression of [[apolipoprotein C3]] and [[PPARGC1B|PPARg coactivator-1b]], thus increasing VLDL-C turnover and reducing its production.<ref>{{cite journal | vauthors = Hernandez C, Molusky M, Li Y, Li S, Lin JD | title = Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid | journal = Cell Metabolism | volume = 12 | issue = 4 | pages = 411–9 | date = October 2010 | pmid = 20889132 | pmc = 2950832 | doi = 10.1016/j.cmet.2010.09.001 }}</ref> Niacin also directly inhibits the action of [[diacylglycerol O-acyltransferase 2]] (DGAT2) a key enzyme for triglyceride synthesis.<ref name=Costet2010/>

The mechanism behind niacin increasing HDL-C is not totally understood, but seems to occur in various ways. Niacin increases [[apolipoprotein A1]] levels by inhibiting the breakdown of this protein, which is a component of HDL-C.<ref>{{cite journal |vauthors=Malik S, Kashyap ML |s2cid=27918392 |title=Niacin, lipids, and heart disease |journal=Curr Cardiol Rep |volume=5 |issue=6 |pages=470–6 |date=November 2003 |pmid=14558989 |doi=10.1007/s11886-003-0109-x }}</ref><ref>{{cite journal | vauthors = Creider JC, Hegele RA, Joy TR | s2cid = 22526314 | title = Niacin: another look at an underutilized lipid-lowering medication | journal = Nature Reviews. Endocrinology | volume = 8 | issue = 9 | pages = 517–28 | date = September 2012 | pmid = 22349076 | doi = 10.1038/nrendo.2012.22 }}</ref> It also inhibits HDL-C hepatic uptake by suppressing production of the [[cholesterol ester transfer protein]] (CETP) gene.<ref name="Villines, T. C. 2012 p 14"/> It stimulates the [[ABCA1|ABCA1 transporter]] in monocytes and macrophages and [[Downregulation and upregulation|upregulates]] [[peroxisome proliferator-activated receptor gamma]], resulting in reverse cholesterol transport.<ref>{{cite journal | vauthors = Rubic T, Trottmann M, Lorenz RL | title = Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin | journal = Biochemical Pharmacology | volume = 67 | issue = 3 | pages = 411–9 | date = February 2004 | pmid = 15037193 | doi = 10.1016/j.bcp.2003.09.014 }}</ref>