Abstract
Niacin is defined collectively as nicotinamide and nicotinic acid, both of which fulfill the vitamin functions of niacin carried out by the bioactive forms NAD(P). In the last few decades numerous new enzymes that consume NAD(P) as substrates have been identified. The functions of these enzymes are emerging as exciting paradigm shifts, even though they are in early stages of discovery. The recent identification of the nicotinic acid receptor has allowed distinction of the drug-like roles of nicotinic acid from its vitamin functions, specifically in modulating blood lipid levels and undesirable side effects such as skin vasodilation and the more rare hepatic toxicities. This information has led to a new strategy for drug delivery for niacin, which, if successful, could have a major impact on human health through decreasing risk for cardiovascular disease. Understanding the many other effects of niacin has much broader potential for disease intervention and treatment in numerous diseases including cancer.
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References
Aktories K, Jakobs KH, Schultz G (1980) Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone – like manner. FEBS Lett 115:11–14
Chinetti-Gbaguidi G, Rigamonti E, Helin L, Mutka AL, Lepore M, Fruchart JC, Clavey V, Ikonen E, Lestavel S, Staels B (2005) Peroxisome proliferator-activated receptor alpha controls cellular cholesterol trafficking in macrophages. J Lipid Res 46:2717–2725
Elvehjem CA, Madden RJ, Strong FM, Woolley DW (1938) The isolation and identification of the anti-black tongue factor. J Biol Chem 123:137–149
Fruchart JC, Duriez P, Staels B (1999) Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol 10:245–257
Fu CS, Swendseid ME, Jacob RA, McKee RW (1989) Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. J Nutr 119:1949–1955
Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126:941–954
Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70:789–829
Kim H, Jacobson EL, Jacobson MK, Lacko AG (2004) Apoa-1 milano and regression of atherosclerosis. JAMA 291:1319
Kontush A, Chantepie S, Chapman MJ (2003) Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress. Arterioscler Thromb Vasc Biol 23:1881–1888
LaRosa JH, LaRosa JC (2000) Enhancing drug compliance in lipid-lowering treatment. Arch Fam Med 9:1169–1175
Lee Y, Yu X, Gonzales F, Mangelsdorf DJ, Wang MY, Richardson C, Witters LA, Unger RH (2002) PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue. Proc Natl Acad Sci USA 99:11848–11853
Lundasen T, Liao W, Angelin B, Rudling M (2003) Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (cyp7a1) in leptin-deficient (ob/ob) mice. J Biol Chem 278:43224–43228
Morgan JM, Capuzzi DM, Baksh RI, Intenzo C, Carey CM, Reese D, Walker K (2003) Effects of extended-release niacin on lipoprotein subclass distribution. Am J Cardiol 91:1432–1436
Myers MG Jr (2004) Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 59:287–304
Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R (2003) Effect of recombinant apoA-I milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290:2292–2300
Offermanns S (2006) The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends Pharmacol Sci 27:384–390
Sasaki J, Yamamoto K, Ageta M (2002) Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: a randomized, double-blind, placebo-controlled, multicenter, crossover study. Clin Ther 24:1614–1626
Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K (2003) Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun 303:364–369
Syvanne M, Nieminen MS, Frick MH, Kauma H, Majahalme S, Virtanen V, Kesaniemi YA, Pasternack A, Ehnholm C, Taskinen MR (1998) Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol. Circulation 98:1993–1999
Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9:352–355
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 (2003) Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem 278:9869–9874
Yoshikawa M, Sakuma N, Hibino T, Sato T, Fujinami T (1997) HDL3 exerts more powerful anti-oxidative, protective effects against copper-catalyzed LDL oxidation than HDL2. Clin Biochem 30:221–225
Yu S, Yarnell JW, Sweetnam P, Bolton CH (2003) High density lipoprotein subfractions and the risk of coronary heart disease: 9-years follow-up in the caerphilly study. Atherosclerosis 166:331–338
Ziegler M (2000) New functions of a long-known molecule. Emerging roles of NAD in cellular signaling. Eur J Biochem 267:1550–1564
Acknowledgments
The research described herein was supported in part by the National Institutes of Health and Niadyne, Inc. ELJ and MKJ are principles in Niadyne, Inc. and conflict of interest management is conducted by the University of Arizona Board of Regents.
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Jacobson, E.L., Kim, H., Kim, M., Jacobson, M. (2012). Niacin: Vitamin and Antidyslipidemic Drug. In: Stanger, O. (eds) Water Soluble Vitamins. Subcellular Biochemistry, vol 56. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2199-9_3
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DOI: https://doi.org/10.1007/978-94-007-2199-9_3
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