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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.
J Pharmacol Exp Ther. 2010 Aug; 334(2):583-9.JP

Abstract

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.

Authors+Show Affiliations

Human Nutrition Research Center of Nantes, Nantes, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20442223

Citation

Le Bloc'h, Jérôme, et al. "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." The Journal of Pharmacology and Experimental Therapeutics, vol. 334, no. 2, 2010, pp. 583-9.
Le Bloc'h J, Leray V, Chetiveaux M, et al. 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. J Pharmacol Exp Ther. 2010;334(2):583-9.
Le Bloc'h, J., Leray, V., Chetiveaux, M., Freuchet, B., Magot, T., Krempf, M., Nguyen, P., & Ouguerram, K. (2010). 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. The Journal of Pharmacology and Experimental Therapeutics, 334(2), 583-9. https://doi.org/10.1124/jpet.110.167478
Le Bloc'h J, et al. 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. J Pharmacol Exp Ther. 2010;334(2):583-9. PubMed PMID: 20442223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Le Bloc'h,Jérôme, AU - Leray,Véronique, AU - Chetiveaux,Maud, AU - Freuchet,Benjamin, AU - Magot,Thierry, AU - Krempf,Michel, AU - Nguyen,Patrick, AU - Ouguerram,Khadija, Y1 - 2010/05/04/ PY - 2010/5/6/entrez PY - 2010/5/6/pubmed PY - 2010/8/18/medline SP - 583 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 334 IS - 2 N2 - 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. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20442223/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_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=20442223 DB - PRIME DP - Unbound Medicine ER -