PT  - JOURNAL ARTICLE
AU  - Jérôme Le Bloc'h
AU  - Véronique Leray
AU  - Maud Chetiveaux
AU  - Benjamin Freuchet
AU  - Thierry Magot
AU  - Michel Krempf
AU  - Patrick Nguyen
AU  - Khadija Ouguerram
TI  - 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
AID  - 10.1124/jpet.110.167478
DP  - 2010 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 583--589
VI  - 334
IP  - 2
4099  - http://jpet.aspetjournals.org/content/334/2/583.short
4100  - http://jpet.aspetjournals.org/content/334/2/583.full
SO  - J Pharmacol Exp Ther2010 Aug 01; 334
AB  - Apolipoprotein B100 (apoB100) is an essential component of very low density lipoprotein (VLDL) and low-density lipoprotein (LDL), both independent markers of cardiovascular risk. Nicotinic acid (NA) is an efficacious drug for decreasing VLDL and LDL, but the underlying mechanisms are unclear. For this purpose, six obese insulin-resistant dogs were given 350 mg/day of NA for 1 week and then 500 mg/day for 3 weeks. Turnover of apoB100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters before and at the end of NA treatment. Hepatic diacylglycerol acyltransferase 2 (DGAT2), microsomal triglyceride transfer protein (MTP), hepatic lipase (HL), and adipose lipoprotein lipase (LPL) mRNA expression was also determined. NA treatment decreased plasma triglyceride (TG) (p < 0.001), VLDL-TG (p < 0.05), total cholesterol (p < 0.0001), and LDL cholesterol (p < 0.05), whereas plasma nonesterified fatty acids were unchanged. The decrease in VLDL-apoB100 concentration (p < 0.001) was the result of a lower absolute production rate (APR) (p < 0.001), despite a moderate decrease (p < 0.05) in fractional catabolic rate (FCR). LDL-apoB100 concentration was reduced (p < 0.05), an effect related to a decrease in LDL APR (p < 0.05) and no change in FCR. NA treatment reduced DGAT2 expression (p < 0.05), whereas MTP, HL, and LPL expression was unchanged. Our results suggest that NA treatment reduced VLDL and LDL concentration as a consequence of a decrease in VLDL production.