Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs

Journal of Pharmacology and Experimental Therapeutics

Volumn 334, Issue 2, 2010, Pages 583-589

  Le Bloc'H, Jérôme ^a,b,c   Leray, Véronique ^a   Chetiveaux, Maud ^a,b   Freuchet, Benjamin ^c   Magot, Thierry ^a,b   Krempf, Michel ^a,b   Nguyen, Patrick ^a,c   Ouguerram, Khadija ^a,b  

^a Human Nutrition Research Center of Nantes   (France)

^b NANTES UNIVERSITY HOSPITAL   (France)

^c LUNAM UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN B100; CHOLESTEROL; DIACYLGLYCEROL ACYLTRANSFERASE 2; FATTY ACID; LIPOPROTEIN LIPASE; LIVER TRIACYLGLYCEROL LIPASE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MESSENGER RNA; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN; NICOTINIC ACID; STABLE ISOTOPE; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CATABOLISM; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOG; ENZYME INHIBITION; FATTY ACID BLOOD LEVEL; INSULIN RESISTANCE; LIVER; MALE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRIACYLGLYCEROL BLOOD LEVEL;

ANIMALS; APOLIPOPROTEIN B-100; DIACYLGLYCEROL O-ACYLTRANSFERASE; DOGS; INSULIN RESISTANCE; KINETICS; LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL; MALE; MODELS, BIOLOGICAL; NIACIN; OBESITY; RNA, MESSENGER;

EID: 77954896506     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.167478     Document Type: Article

References (36)

1. Bailhache E, Briand F, Nguyen P, Krempf M, Magot T, and Ouguerram K (2004) Metabolism of cholesterol ester of apolipoprotein B100-containing lipoproteins in dogs: evidence for disregarding cholesterol ester transfer. Eur J Clin Invest 34: 527-534.
2. Bailhache E, Nguyen P, Krempf M, Siliart B, Magot T, and Ouguerram K (2003a) Lipoproteins abnormalities in obese insulin-resistant dogs. Metabolism 52:559-564.
3. Bailhache E, Ouguerram K, Gayet C, Krempf M, Siliart B, Magot T, and Nguyen P (2003b) An insulin-resistant hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the euglycaemic hyperinsulinaemic clamp in combination with the stable isotope technique. J Anim Physiol Anim Nutr (Berl) 87:86-95.
4. Blackard WG and Heidingsfelder SA (1969) Effect of adrenergic receptor blackade on nicotinic acid-induced plasma FFA rebound. Metabolism 18:226-233.
5. Briand F, Bailhache E, Andre A, Magot T, Krempf M, Nguyen P, and Ouguerram K (2008) The hyperenergetic-fed obese dog, a model of disturbance of apolipoprotein B-100 metabolism associated with insulin resistance: kinetic study using stable isotopes. Metabolism 57:966-972.
6. Brown BG and Zhao XQ (2008) Nicotinic acid, alone and in combinations, for reduction of cardiovascular risk. Am J Cardiol 101:58B-62B.
7. Bruce KD and Hanson MA (2010) The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 140:648-652.
8. Choi CS, Savage DB, Kulkarni A, Yu XX, Liu ZX, Morino K, Kim S, Distefano A, Samuel VT, Neschen S, et al. (2007) Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance. J Biol Chem 282:22678-22688.
9. Cobelli C, Toffolo G, and Foster DM (1992) Tracer-to-tracee ratio for analysis of stable isotope tracer data: link with radioactive kinetic formalism. Am J Physiol 262:E968-E975.
10. Dhalla AK, Santikul M, Smith M, Wong MY, Shryock JC, and Belardinelli L (2007) Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid. J Pharmacol Exp Ther 321:327-333. (Pubitemid 46456970)
11. Duvillard L, Pont F, Florentin E, Galland-Jos C, Gambert P, and Vergès B (2000) Metabolic abnormalities of apolipoprotein B-containing lipoproteins in noninsulin- dependent diabetes: a stable isotope kinetic study. Eur J Clin Invest 30:685-694.
12. Fabbrini E, Mohammed BS, Korenblat KM, Magkos F, McCrea J, Patterson BW, and Klein S (2010) Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoproteins kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab 95:2727-2735.
13. Ganji SH, Tavintharan S, Zhu D, Xing Y, Kamanna VS, and Kashyap ML (2004) Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res 45:1835-1845.
14. Gille A, Bodor ET, Ahmed K, and Offermanns S (2008) Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol 48:79-106.
15. Goldberg A, Alagona P Jr, Capuzzi DM, Guyton J, Morgan JM, Rodgers J, Sachson R, and Samuel P (2000) Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 85:1100-1105.
16. Grundy SM, Vega GL, McGovern ME, Tulloch BR, Kendall DM, Fitz-Patrick D, Ganda OP, Rosenson RS, Buse JB, Robertson DD, et al. (2002) Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med 162:1568-1576.
17. Jin FY, Kamanna VS, and Kashyap ML (1999) Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol 19:1051-1059.
18. Kabir M, Catalano KJ, Ananthnarayan S, Kim SP, Van Citters GW, Dea MK, and Bergman RN (2005) Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance. Am J Physiol Endocrinol Metab 288:E454-E461.
19. Kamanna VS and Kashyap ML (2008) Mechanism of action of niacin. Am J Cardiol 101:20B-26B.
20. Lamon-Fava S, Diffenderfer MR, Barrett PH, Buchsbaum A, Nyaku M, Horvath KV, Asztalos BF, Otokozawa S, Ai M, Matthan NR, et al. (2008) Extended-release niacin alters the metabolism of plasma apolipoprotein (Apo) A-I and ApoB-containing lipoproteins. Arterioscler Thromb Vasc Biol 28:1672-1678.
21. Maugeais C, Ouguerram K, Frénais R, Maugère P, Charbonnel B, Magot T, and Krempf M (2001) Effect of low-density lipoprotein apheresis on kinetics of apolipoprotein B in heterozygous familial hypercholesterolemia. J Clin Endocrinol Metab 86:1679-1686. (Pubitemid 32374923)
22. Meyers CD and Kashyap ML (2004) Management of the metabolic syndrome-nicotinic acid. Endocrinol Metab Clin North Am 33:557-575.
23. Ouguerram K, Magot T, Zaïr Y, Marchini JS, Charbonnel B, Laouenan H, and Krempf M (2003) Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes. J Pharmacol Exp Ther 306:332-337.
24. Ouguerram K, Nguyen P, Krempf M, Pouteau E, Briand F, Bailhache E, and Magot T (2004) Selective uptake of high density lipoproteins cholesteryl ester in the dog, a species lacking in cholesteryl ester transfer protein activity; An in vivo approach using stable isotopes. Comp Biochem Physiol B Biochem Mol Biol 138:339-345.
25. Pont F, Duvillard L, Florentin E, Gambert P, and Vergès B (2002) Early kinetic abnormalities of apoB-containing lipoproteins in insulin-resistant women with abdominal obesity. Arterioscler Thromb Vasc Biol 22:1726-1732.
26. Radziuk J (2000) Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab 85:4426-4433.
27. Serisier S, Gayet C, Leray V, Le Bloc'h J, Ouguerram K, Magot T, and Nguyen P (2008) Hypertriglyceridaemic insulin-resistant obese dog model: effects of high-fat diet depending on age. J Anim Physiol Anim Nutr (Berl) 92:419-425.
28. Svedmyr N, Harthon L, and Lundholm L (1969) The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man. Clin Pharmacol Ther 10:559-570.
29. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, and Grace KA (2004) Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 110:3512-3517.
30. Tenenbaum A, Fisman EZ, Motro M, and Adler Y (2006) Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. Cardiovasc Diabetol 5:20.
31. Vega GL, Cater NB, Meguro S, and Grundy SM (2005) Influence of extended-release nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia. Am J Cardiol 95:1309-1313.
32. Wang W, Basinger A, Neese RA, Christiansen M, and Hellerstein MK (2000) Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of glucose production in women. Am J Physiol Endocrinol Metab 279:E50-59.
33. Wang W, Basinger A, Neese RA, Shane B, Myong SA, Christiansen M, and Hellerstein MK (2001) Effect of nicotinic acid administration on hepatic very low density lipoprotein-triglyceride production. Am J Physiol Endocrinol Metab 280:E540-E547.
34. Wolfgang GH, Robertson DG, Welty DF, and Metz AL (1995) Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs. Fundam Appl Toxicol 26:272-281.
35. Yao Z and McLeod RS (1994) Synthesis and secretion of hepatic apolipoprotein B-containing lipoproteins. Biochim Biophys Acta 1212:152-166.
36. Zammit VA, Buckett LK, Turnbull AV, Wure H, and Proven A (2008) Diacylglycerol acyltransferases: Potential roles as pharmacological targets. Pharmacol Ther 118: 295-302.