综述 REVIEW

烟酸的功能及其在脂肪代谢中的作用机制

  • 钟港 ,
  • 苏敏超 ,
  • 王笑言 ,
  • 陈东
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  • 湖南农业大学动物科学技术学院, 长沙 410128
钟港(1997—),男,湖南醴陵人,硕士研究生,从事反刍动物营养与饲料研究。E-mail:861149076@qq.com

收稿日期: 2022-03-06

  网络出版日期: 2022-10-17

基金资助

国家自然科学基金青年基金项目(32002202);湖南省教育厅科学研究项目重点项目(19A237);湖南省草食动物产业技术体系

Functions of Nicotinic Acid and Its Mechanism in Fat Metabolism

  • ZHONG Gang ,
  • SU Minchao ,
  • WANG Xiaoyan ,
  • CHEN Dong
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  • College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China

Received date: 2022-03-06

  Online published: 2022-10-17

摘要

烟酸是辅酶烟酰胺腺嘌呤二核苷酸(NAD)和烟酰胺腺嘌呤二核苷酸磷酸(NADP)的前体物质。近年来研究发现,烟酸是一种多功能物质,对动物机体健康有积极的影响。本文主要介绍了烟酸在保护神经系统、抗炎症和调节脂肪代谢等方面的功能,重点从烟酸和烟酸受体介导的信号通路2方面探讨了烟酸调节机体脂肪代谢的分子机制,以期为烟酸的科学应用提供理论依据。

本文引用格式

钟港 , 苏敏超 , 王笑言 , 陈东 . 烟酸的功能及其在脂肪代谢中的作用机制[J]. 动物营养学报, 2022 , 34(9) : 5516 -5525 . DOI: 10.3969/j.issn.1006-267x.2022.09.007

Abstract

Nicotinic acid is a precursor of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Recent studies have found that nicotinic acid is a multifunctional substance and has positive effects on animal health. In this paper we mainly discussed the functions of nicotinic acid in protecting the nervous system, anti-inflammation and regulating fat metabolism. The molecular mechanism of nicotinic acid regulating fat metabolism was discussed from two aspects of nicotinic acid and nicotinic acid receptor mediated signaling pathway, in order to provide a theoretical basis for the scientific application of nicotinic acid.

参考文献

[1] GILLE A, BODOR E T, AHMED K, et al.Nicotinic acid:pharmacological effects and mechanisms of action[J].Annual Review of Pharmacology and Toxicology, 2008, 48:79-106.
[2] 李慧瑾, 金曦, 李鹏权, 等.烟酸和烟酸受体激动剂在动脉粥样硬化中的研究进展[J].中国药理学通报, 2020, 36(10):1341-1345. LI H J, JIN X, LI P Q, et al.Research progress on niacin and niacin receptor agonists in atherosclerosis[J].Chinese Pharmacological Bulletin, 2020, 36(10):1341-1345.(in Chinese)
[3] GRAFF E C, FANG H, WANDERS D, et al.The absence of adiponectin alters niacin's effects on adipose tissue inflammation in mice[J].Nutrients, 2020, 12(8):2427.
[4] KASHYAP M L, GANJI S, NAKRA N K, et al.Niacin for treatment of nonalcoholic fatty liver disease (NAFLD):novel use for an old drug?[J].Journal of Clinical Lipidology, 2019, 13(6):873-879.  
[5] ROBERTS W C.From the editor pellagra, osler, roberts, goldberger, the atherosclerotic diet, niacin, the beginning of the atherosclerotic epidemic, and the first lipid-altering drug[J].The American Journal of Cardiology, 2019, 123(4):697-700.  
[6] SCHANDELMAIER S, BRIEL M, SACCILOTTO R, et al.Niacin for primary and secondary prevention of cardiovascular events[J].Cochrane Database of Systematic Reviews, 2017, 6(6):CD009744.
[7] KUMAR A, SINGH A, Ekavali.A review on Alzheimer's disease pathophysiology and its management:an update[J].Pharmacological Reports, 2015, 67(2):195-203.  
[8] WILLIAMS A C, HILL L J, RAMSDEN D B.Nicotinamide, NAD(P)(H), and methyl-group homeostasis evolved and became a determinant of ageing diseases:hypotheses and lessons from pellagra[J].Current Gerontology and Geriatrics Research, 2012, 2012:302875.
[9] MORRIS M C, EVANS D A, BIENIAS J L, et al.Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline[J].Journal of Neurology, Neurosurgery, and Psychiatry, 2004, 75(8):1093-1099.  
[10] AASETH J, DUSEK P, ROOS P M.Prevention of progression in Parkinson's disease[J].BioMetals, 2018, 31(5):737-747.  
[11] WAKADE C, CHONG R, BRADLEY E, et al.Upregulation of GPR109A in Parkinson's disease[J].PLoS One, 2014, 9(10):e109818.
[12] WAKADE C, GIRI B, MALIK A, et al.Niacin modulates macrophage polarization in Parkinson's disease[J].Journal of Neuroimmunology, 2018, 320:76-79.
[13] CUI X, CHOPP M, ZACHAREK A, et al.Niacin treatment of stroke increases synaptic plasticity and axon growth in rats[J].Stroke, 2010, 41(9):2044-2049.  
[14] KWON W Y, SUH G J, KIM K S, et al.Niacin suppresses the mitogen-activated protein kinase pathway and attenuates brain injury after cardiac arrest in rats[J].Critical Care Medicine, 2013, 41(9):e223-e232.
[15] GHANIM H, ALJADA A, HOFMEYER D, et al.Circulating mononuclear cells in the obese are in a proinflammatory state[J].Circulation, 2004, 110(12):1564-1571.  
[16] WANDERS D, GRAFF E C, WHITE B D, et al.Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice[J].PLoS One, 2013, 8(8):e71285.
[17] SUBRAMANI K, CHU X G, WARREN M, et al.Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock[J].Biochimica et Biophysica Acta:Molecular Basis of Disease, 2019, 1865(3):688-695.  
[18] WU B J, YAN L, CHARLTON F, et al.Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction Independent of changes in plasma lipids[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, 30(5):968-975.  
[19] DIGBY J E, MARTINEZ F, JEFFERSON A, et al.Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2012, 32(3):669-676.  
[20] ZHANG B B, HAO J Z, YIN H J, et al.Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese[J].Poultry Science, 2021, 100(11):101430.
[21] ADEBOWALE T O, LIU H N, OSO A O, et al.Effect of dietary niacin supplementation on performance, total tract nutrient retention, carcass yield and meat lipid profile of growing turkeys[J].Animal Production Science, 2018, 59(6):1098-1107.
[22] ADEBOWALE T, OSO A, LIU H N, et al.Effect of dietary niacin supplementation on growth performance, nutrient digestibility, hematology, and lipoprotein concentrations of young turkeys, Meleagris gallopavo[J].The Journal of Poultry Science, 2019, 56(2):112-119.  
[23] YANG Z Q, BAO L B, ZHAO X H, et al.Nicotinic acid supplementation in diet favored intramuscular fat deposition and lipid metabolism in finishing steers[J].Experimental Biology and Medicine, 2016, 241(11):1195-1201.  
[24] YANG Z Q, ZHAO X H, XIONG X W, et al.Uncovering the mechanism whereby dietary nicotinic acid increases the intramuscular fat content in finishing steers by RNA sequencing analysis[J].Animal Production Science, 2019, 59(9):1620-1630.  
[25] 王雪莹.烟酸对牦牛热应激期生长性能、营养物质表观消化率和脂质代谢的影响[D].硕士学位论文.雅安:四川农业大学, 2019. WANG X Y.Effects of niacin on grouth performance, apparent digestibility of nutrients and lipid metabolism in yak under heat-stress[D].Master's Thesis.Ya'an:Sichuan Agricultural University, 2019.(in Chinese)
[26] HRISTOVSKA T, CINCOVIĆ M R, BELIĆ B, et al.Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation[J].Acta Veterinaria Brno, 2017, 86(3):231-238.  
[27] PIRES J A A, STUMPF L F, SOUTULLO I D, et al.Effects of abomasal infusion of nicotinic acid on responses to glucose and β-agonist challenges in underfed lactating cows[J].Journal of Dairy Science, 2016, 99(3):2297-2307.  
[28] KHAN M, RINGSEIS R, MOOREN F C, et al.Niacin supplementation increases the number of oxidative type Ⅰ fibers in skeletal muscle of growing pigs[J].BMC Veterinary Research, 2013, 9:177.
[29] LIU L, LI C Y, FU C Y, et al.Dietary niacin supplementation suppressed hepatic lipid accumulation in rabbits[J].Asian-Australasian Journal of Animal Sciences, 2016, 29(12):1748-1755.  
[30] LI X F, WANG T J, QIAN Y, et al.Dietary niacin requirement of juvenile blunt snout bream Megalobrama amblycephala based on a dose-response study[J].Aquaculture Nutrition, 2017, 23(6):1410-1417.  
[31] OOI E M, WATTS G F, CHAN D C, et al.Effects of extended-release niacin on the postprandial metabolism of Lp (a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, 35(12):2686-2693.  
[32] MOSELHY S S, KAMAL I H, KUMOSANI T A, et al.Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol:as targeting for hypocholesterolemic action[J].African Health Sciences, 2016, 16(1):319-324.  
[33] ROMANI M, HOFER D C, KATSYUBA E, et al.Niacin:an old lipid drug in a new NAD+ dress[J].Journal of Lipid Research, 2019, 60(4):741-746.  
[34] MONETTI M, LEVIN M C, WATT M J, et al.Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver[J].Cell Metabolism, 2007, 6(1):69-78.  
[35] UMAYAHARA Y, KAJIMOTO Y, FUJITANI Y, et al.Protein kinase C-dependent, CCAAT/enhancer-binding protein beta-mediated expression of insulin-like growth factor Ⅰ gene[J].Journal of Biological Chemistry, 2002, 277(18):15261-15270.  
[36] TAN S H, SHUI G H, ZHOU J, et al.Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin)[J].Journal of Biological Chemistry, 2012, 287(18):14364-14376.  
[37] GANJI S H, KASHYAP M L, KAMANNA V S.Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes:impact on non-alcoholic fatty liver disease[J].Metabolism, 2015, 64(9):982-990.  
[38] GANJI S H, TAVINTHARAN S, ZHU D M, et al.Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells[J].Journal of Lipid Research, 2004, 45(10):1835-1845.  
[39] HU M, CHU W C W, YAMASHITA S, et al.Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients[J].Journal of Lipid Research, 2012, 53(4):802-809.  
[40] BONYADI M, MOHAMMADIAN T, RAFEEY M, et al.Chemokine MCP1/CCL2 gene polymorphism influences Henoch-Schönlein purpura susceptibility in Iranian Azeri-Turkish patients[J].International Journal of Dermatology, 2015, 54(11):1269-1274.  
[41] 邢雪琨, 武红艳, 林俊堂, 等.趋化因子2促进肝再生中脂肪的形成[J].解剖学报, 2016, 47(5):697-702. XING X K, WU H Y, LIN J T, et al.Effect of chemokine 2 on the formation of lipid on liver regeneration[J].Acta Anatomica Sinica, 2016, 47(5):697-702.(in Chinese)
[42] XING X K, WANG H, ZHAO L, et al.Niacin downregulates chemokine (c-c motif) ligand 2(CCL2) expression and inhibits fat synthesis in rat liver cells[J].Tropical Journal of Pharmaceutical Research, 2020, 19(5):977-982.  
[43] KROON T, BACCEGA T, OLSÉN A, et al.Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats[J].Journal of Lipid Research, 2017, 58(1):31-41.  
[44] 欧露, 麻燕妮, 张彩平, 等.烟酸通过下调PCSK9的表达促进HepG2细胞摄取LDL-C[J].中国药理学通报, 2017, 33(2):243-248. OU L, MA Y N, ZHANG C P, et al.Niacin accelerates LDL-C uptake in HepG2 cells via downregulation of PCSK9[J].Chinese Pharmacological Bulletin, 2017, 33(2):243-248.(in Chinese)
[45] MANGAT R, BORTHWICK F, HAASE T, et al.Intestinal lymphatic HDL miR-223 and ApoA-Ⅰ are reduced during insulin resistance and restored with niacin[J].FASEB Journal, 2018, 32(3):1602-1612.  
[46] RINGSEIS R, ROSENBAUM S, GESSNER D K, et al.Supplementing obese Zucker rats with niacin induces the transition of glycolytic to oxidative skeletal muscle fibers[J].Journal of Nutrition, 2013, 143(2):125-131.  
[47] YE L Y, CAO Z, LAI X R, et al.Niacin ameliorates hepatic steatosis by inhibiting de novo lipogenesis via a GPR109A-mediated PKC-ERK1/2-AMPK signaling pathway in C57BL/6 mice fed a high-fat diet[J].The Journal of Nutrition, 2020, 150(4):672-684.  
[48] YE L Y, CAO Z, LAI X R, et al.Niacin fine-tunes energy homeostasis through canonical GPR109A signaling[J].FASEB Journal, 2019, 33(4):4765-4779.  
[49] ADEPU K K, KACHHAP S, ANISHKIN A, et al.Structural and energetic insights into the interaction of niacin with the GPR109A receptor[J].Bioinformatics and Biology Insights, 2021, 15:11779322211056122.
[50] KOPP C, HOSSEINI A, SINGH S P, et al.Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling[J].International Journal of Molecular Sciences, 2014, 15(11):21401-21418.  
[51] PLAISANCE E P, LUKASOVA M, OFFERMANNS S, et al.Niacin stimulates adiponectin secretion through the GPR109A receptor[J].American Journal of Physiology:Endocrinology and Metabolism, 2009, 296(3):E549-E558.
[52] MASUDA Y, KURIKAWA N, NISHIZAWA T.Overexpressing human GPR109A leads to pronounced reduction in plasma triglyceride levels in BAC transgenic rats[J].Atherosclerosis, 2018, 272:182-192.
[53] JADEJA R N, JONES M A, FROMAL O, et al.Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis[J].Aging, 2019, 11(2):386-400.  
[54] LAGE R, DIÉGUEZ C, VIDAL-PUIG A, et al.AMPK:a metabolic gauge regulating whole-body energy homeostasis[J].Trends in Molecular Medicine, 2008, 14(12):539-549.  
[55] SWITON K, KOTULSKA K, JANUSZ-KAMINSKA A, et al.Molecular neurobiology of mTOR[J].Neuroscience, 2017, 341:112-153.
[56] YIN F, SHAREN G, YUAN F, et al.TIP30 regulates lipid metabolism in hepatocellular carcinoma by regulating SREBP1 through the Akt/mTOR signaling pathway[J].Oncogenesis, 2017, 6(6):e347.
[57] MAGNUSON B, EKIM B, FINGAR D C.Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks[J].Biochemical Journal, 2012, 441(1):1-21.  
[58] WANG J X, CAO Y, FU S P, et al.Niacin inhibits the synthesis of milk fat in BMECs through the GPR109A-mediated downstream signalling pathway[J].Life Sciences, 2020, 260:118415.
[59] GASIC S, TIAN B, GREEN A.Tumor necrosis factor α stimulates lipolysis in adipocytes by decreasing Gi protein concentrations[J].Journal of Biological Chemistry, 1999, 274(10):6770-6775.  
[60] CHEN L H, SO W Y, LI S Y T, et al.Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets[J].Molecular and Cellular Endocrinology, 2015, 404:56-66.
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