Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells

Journal of Lipid Research

Volumn 45, Issue 10, 2004, Pages 1835-1845

  Ganji, Shobha H ^a   Tavintharan, S ^a   Zhu, Daming ^a   Xing, Yiding ^a   Kamanna, Vaijinath S ^a   Kashyap, Moti L ^a  

^a NONE

Author keywords

Diacylglycerol acyltransferase; Hepatocytes; Lipoproteins; Triglyceride

Indexed keywords

2 CYANO N (4 CYANOPHENYL) 3 CYCLOPROPYL 3 OXOPROPIONAMIDE; ANTILIPEMIC AGENT; DIACYLGLYCEROL ACYLTRANSFERASE; DIACYLGLYCEROL ACYLTRANSFERASE 1; DIACYLGLYCEROL ACYLTRANSFERASE 2; GLYCEROL 1,2 DIOLEATE; GLYCEROL DERIVATIVE; LIPOPROTEIN; NICOTINIC ACID; OLEOYL COENZYME A; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ACYLTRANSFERASE; DGAT1 PROTEIN, HUMAN; DGAT2 PROTEIN, HUMAN; MESSENGER RNA;

ARTICLE; ATHEROGENESIS; CELL STRAIN HEPG2; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG SELECTIVITY; DYSLIPIDEMIA; ENZYME INHIBITION; ENZYME KINETICS; ENZYME SUBSTRATE; GENE EXPRESSION; HUMAN; HUMAN CELL; IC 50; LIPOGENESIS; LIVER MICROSOME; PRIORITY JOURNAL; PROTEIN SECRETION; BIOSYNTHESIS; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; KINETICS; LIVER CELL; METABOLISM; SECRETION; TUMOR CELL LINE;

ACYLTRANSFERASES; CELL LINE, TUMOR; DIACYLGLYCEROL O-ACYLTRANSFERASE; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HEPATOCYTES; HUMANS; KINETICS; LIPOPROTEINS; NIACIN; RNA, MESSENGER; TRIGLYCERIDES;

EID: 16644369497     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: 10.1194/jlr.M300403-JLR200     Document Type: Article

References (43)

1. Carlson, L. A., and L. Oro. 1973. Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia. Atherosclerosis. 18: 1-9.
2. Tavintharan, S., and M. L. Kashyap. 2001. The benefits of niacin in atherosclerosis. Curr. Atheroscler. Rep. 3: 74-82.
3. Capuzzi, D. M., J. R. Guyton, and J. M. Morgan. 1998. Efficacy and safety of extended-release niacin (Niaspan): a long-term study. Am. J. Cardiol. 82: 74U-81U.
4. Canner, P. L., K. G. Berge, and N. K. Wanger. 1986. Fifteen years mortality in coronary drug project patients. Long term benefit with niacin. J. Am. Coll. Cardiol. 8: 1245-1255.
5. Blankenhorn, D. H., S. A. Nessim, R. L. Johnson, M. E. Sammarco, S. P. Azen, and L. Cashin-Hemphill. 1987. Beneficial effects of combined colestipol, niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. J. Am. Med. Assoc. 247: 3233-3240.
6. Brown, B. G., X. Q. Zhao, A. Chait, L. D. Fisher, M. C. Cheung, J. S. Morse, A. A. Dowdy, E. K. Marino, E. L. Bolson, P. Alaupovic, J. Frohlich, and J. J. Albers. 2001. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N. Engl. J. Med. 345: 1583-1592.
7. Jin, F. Y., V. S. Kamanna, and M. L. Kashyap. 1999. Niacin accelerates intracellular apo B degradation by inhibiting triglyceride synthesis in human hepatoblastoma (HepG2) cells. Arterioscler. Thromb. Vasc. Biol. 19: 1051-1059.
8. Kamanna, V. S., and M. L. Kashyap. 2000. Mechanism of action of niacin on lipoprotein metabolism. Curr. Atheroscler. Rep. 2: 36-46.
9. Dixon, J. L., and H. N. Ginsberg. 1993. Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells. J. Lipid Res. 34: 167-179.
10. Davis, R. A. 1999. Cell and molecular biology of the assembly and secretion of apolipoprotein B containing lipoproteins by the liver. Biochim. Biophys. Acta. 1440: 1-31.
11. Grundy, S. M., H. Y. Mok, L. Zech, and M. Berman. 1981. Influence of nicotinic acid on metabolism of cholesterol and triglyceride in man. J. Lipid Res. 22: 24-36.
12. Cases, S., S. J. Smith, Y. W. Zheng, H. M. Myers, S. R. Lear, E. Sande, S. Novak, C. Collins, C. B. Welch, A. J. Lusis, S. K. Erickson, and R. V. Farese, Jr. 1998. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triglyceride synthesis. Proc. Natl. Acad. Sci. USA. 95: 13018-13023.
13. Liang, J. S., P. M. Oelkers, P. C. Chu, H. N. Ginsberg, and S. L. Sturley. 1999. Overexpression of human diacylglycerol acyltransferase results in increased triglyceride synthesis and increased secretion of apoB-containing lipoproteins (Abstract). Circulation. 100 (Suppl.): 3615A.
14. Cases, S., S. J. Stone, P. Zhou, E. Yen, B. Tow, K. D. Lardizabal, T. Voelker, and R. V. Farese, Jr. 2001. Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J. Biol. Chem. 276: 38870-38876.
15. Oelkers, P., A. Behari, D. Cromely, J. T. Billheimer, and S. L. Sturley. 1998. Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. J. Biol. Chem. 273: 26765-26771.
16. Owen, M. R., C. C. Corstorphine, and V. A. Zammit. 1997. Overt and latent activities of diacylglycerol acyltransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem. J. 323: 17-21.
17. Waterman, I. J., and V. A. Zammit. 2002. Differential effects of fenofibrate or simvastatin treatment of rats on hepatic microsomal overt and latent diacylglycerol acyltransferase activities. Diabetes. 51: 1708-1713.
18. Yang, L. Y., A. Kuksis, J. J. Myher, and G. Steiner. 1995. Origin of triacylglycerol moiety of plasma very low density lipoprotein in the rat: structural studies. J. Lipid Res. 37: 125-136.
19. Grigor, M. R., and R. M. Bell. 1982. Separate monoacylglycerol and diacylglycerol acyltransferases function in intestinal triglyceride synthesis. Biochim. Biophys. Acta. 712: 464-472.
20. Coleman, R. A. 1992. Diacylglycerol acyltransferase and monoacylglycerol acyltransferase from liver and intestine. Methods Enzymol. 209: 98-104.
21. Coleman, R. A., and E. B. Haynes. 1986. Monoacylglycerol acyltransferase, evidence that the activities from rat intestine and suckling liver are tissue specific isoenzymes. J. Biol. Chem. 261: 224-228.
22. Parkes, J. G., and W. Thompson. 1970. The composition of phospholipids in outer and inner mitochondrial membranes from guinea-pig liver. Biochim. Biophys. Acta. 196: 162-169.
23. Chen, H. C., S. J. Smith, Z. Ladha, D. R. Jensen, L. D. Ferreira, L. K. Pulawa, J. G. McGuire, R. E. Pitas, R. H. Eckel, and R. V. Farese, Jr. 2002. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J. Clin. Invest. 109: 1049-1055.
24. Owen, M., and V. A. Zammit. 1997. Evidence for overt and latent forms of DGAT in rat liver microsomes. Implications for the pathways of triacylglycerol incorporation into VLDL (Abstract). Biochem. Soc. Trans. 25 (Suppl.): 21.
25. Bell, R. M. 1980. Enzymes of glycerolipid synthesis in eukaryotes. Annu. Rev. Biochem. 49: 459-487.
26. Mayorek, N., I. Grinstein, and J. Bar-Tana. 1989. Triacylglycerol synthesis in cultured rat hepatocytes. The rate-limiting role of diacylglycerol acyltransferase. Eur. J. Biochem. 182: 395-400.
27. Rustan, A. C., J. O. Nossen, E. N. Christiansen, and C. A. Drevon. 1988. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triglyceride by decreasing the activity of acyl-coenzyme A: 1,2-diacylglycerol acyltransferase. J. Lipid Res. 29: 1417-1426.
28. Stals, H. K., W. Top, and P. E. Declercq. 1994. Regulation of triglyceride synthesis in permeabilized rat hepatocytes. Role of fatty acid concentration and diacylglycerol acyltransferase. FEBS Lett. 343: 99-102.
29. Coleman, R. A., P. Rao, R. J. Fogelsong, and E. S-G. Bardes. 1992. 2-Bromopalmitoyl-CoA and 2-bromopalmitate: Promiscuous inhibitors of membrane-bound enzymes. Biochim. Biophys. Acta. 1125: 203-209.
30. Akao, T., and T. Kusaka. 1976. Solubilization of diglyceride acyltransferase from the membrane of Mycobacterium smegmatis. J. Biochem. (Tokyo). 80: 723-728.
31. Polokoff, M. A., and R. M. Bell. 1980. Solubilization, partial purification and characterization of rat liver microsomal diacylglycerol acyltransferase. Biochim. Biophys. Acta. 618: 129-142.
32. Buhman, K. K., S. J. Smith, S. J. Stones, J. J. Repa, J. S. Wong, F. F. Knapp, Jr., B. J. Burri, R. L. Hamilton, N. A. Abumrad, and R. V. Farese, Jr. 2002. DGAT1 is not essential for intestinal triacylglycerol absorption or chylomicron synthesis. J. Biol. Chem. 277: 25474-25479.
33. Smith, S. J., S. Cases, D. R. Jensen, H. C. Chen, E. Sande, T. Bow, D. A. Sanen, J. Raber, R. H. Eckel, and R. V. Farese, Jr. 2000. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat. Genet. 25: 87-90.
34. Meegalla, R. L., J. T. Billheimer, and D. Cheng. 2002. Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin. Biochem. Biophys. Res. Commun. 298: 317-323.
35. Lankester, D., A. Brown, and V. Zammit. 1998. Use of cytosolic triacylglycerol hydrolysis products and of exogenous fatty acids for the synthesis of triacylglycerol secreted by cultured hepatocytes. J. Lipid Res. 32: 1635-1645.
36. Dixon, J. L., S. Furukawa, and H. N. Ginsberg. 1991. Oleate stimulates secretion of apolipoprotein B containing lipoproteins from Hep G2 cells by inhibiting early intracellular degradation of apolipoprotein B. J. Biol. Chem. 266: 5080-5086.
37. Wu, X., N. Sakata, J. L. Dixon, and H. N. Ginsberg. 1994. Exogenous VLDL stimulates apolipoprotein from Hep G2 cells by both pre- and post-translational mechanisms. J. Lipid Res. 35: 1200-1210.
38. Benoist, F., and T. Grand-Perret. 1996. ApoB-100 secretion by HepG2 cells is regulated by the rate of triglyceride biosynthesis but not by intracellular lipid pools. Arterioscler. Thromb. Vasc. Biol. 16: 1229-1235.
39. Carlson, L. A., and L. Oro. 1962. The effect of nicotinic acid on plasma free fatty acids. Demonstration of a metabolic type of sympathicolysis. Acta Med. Scand. 172: 641-645.
40. Carlson, L. A. 1963. Studies on the effect of nicotinic acid on catecholamine stimulated lipolysis in adipose tissue in vitro. Acta Med. Scand. 173: 710-722.
41. Lee, H. M., R. M. Ellis, and M. V. Signal, Jr. 1961. Some insulin-like effects of nicotinic acid observed with isolated rat epididymal adipose tissue. Biochim. Biophys. Acta. 49: 408-410.
42. Tunaru, S., J. Kero, A. Schaub, C. Wufka, A. Blaukat, K. Pfeffer, and S. Offermanns. 2003. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat. Med. 9: 352-355.
43. Wise, A., S. M. Foord, N. J. Fraser, A. A. Barnes, N. Elshourbagy, M. Eilert, D. M. Ignar, P. R. Murdock, K. Steplewski, A. Green, A. J. Brown, S. J. Dowell, P. G. Szekeres, D. G. Hassall, F. H. Marshall, S. Wilson, and N. B. Pike. 2003. Molecular identification of high and low affinity receptors for nicotinic acid. J. Biol. Chem. 278: 9869-9874.