Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs.

Aim: Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden.

Low rate of production of apolipoproteins B100 and AI in 2 patients with Anderson disease (chylomicron retention disease).

Objective: Anderson disease is a rare inherited lipid malabsorption syndrome associated with hypocholesterolemia and linked to SAR1B mutations. The aim of this article was to analyze the mechanisms responsible for the low plasma apolipoprotein Apo-B100 and Apo-AI in 2 patients with Anderson disease.

Methods And Results: A primed constant infusion of (13)C-leucine was administered for 14 hours to determine the kinetics of lipoproteins.

Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters.

Background: Reverse cholesterol transport (RCT) is an anti-atherogenic process by which cholesterol is effluxed from peripheral tissues by high-density lipoprotein (HDL) and returned to the liver for excretion into the bile and faeces. Dyslipidemia is thought to impair RCT through higher triglyceride-rich lipoprotein (TRL), low HDL-cholesterol and higher activity of cholesteryl ester transfer protein (CETP), which transfers cholesteryl esters from HDL to TRL for further hepatic uptake. As CETP pathway would represent a major route in human RCT, we therefore investigated whether diet-induced dyslipidemia impairs RCT in hamster, a CETP-expressing species.

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.

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.

The hyperenergetic-fed obese dog, a model of disturbance of apolipoprotein B-100 metabolism associated with insulin resistance: kinetic study using stable isotopes.

The hyperenergetic-fed beagle dog model of obesity-associated insulin resistance has previously demonstrated lipoprotein abnormalities similar to those of obese insulin-resistant humans. The aim of this study was to check, in the insulin-resistant dog, the mechanism leading to abnormalities in the mass of apolipoprotein B-100 (apo B-100) containing lipoproteins. Six healthy male beagle dogs were overfed with a high-fat diet for 28 +/- 2.

Effects of green tea on insulin sensitivity, lipid profile and expression of PPARalpha and PPARgamma and their target genes in obese dogs.

As in man, canine obesity is associated with insulin resistance, dyslipidaemia and other chronic diseases. This study was designed to examine the effects of a nutritional supplement (green tea) on insulin sensitivity and plasma lipid concentrations in an obese insulin-resistant dog model. We also determined mRNA expression of two transcription factors, PPARgamma and PPARalpha, and some of their target genes, including GLUT4, lipoprotein lipase (LPL) and adiponectin.

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.

Amongst the processes involved in the reverse cholesterol transport (RCT) from organs to liver, including high density lipoproteins-apolipoprotein AI (HDL-apoAI) dependent tissue uptake and cholesteryl ester transfer protein (CETP)-mediated transfers, the selective uptake of cholesteryl ester (CE) is of increasing interest through its antiatherogenic role. The purpose of this report is to develop a simple protocol allowing study of this process in an animal model with easier quantification of CE selective uptake. The dog was chosen essentially because this animal has a low CETP activity and an appropriate size to conduce a kinetic study.

Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9.

Objective: We have reported further heterogeneity in familial autosomal-dominant hypercholesterolemia (FH) related to mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form of hypercholesterolemia.

Methods And Results: In vivo kinetics of apolipoprotein B100-containing lipoproteins using a 14-hour primed constant infusion of [2H3] leucine was conducted in 2 subjects carrying the mutation S127R in PCSK9, controls subjects, and FH subjects with known mutations on the low-density lipoprotein (LDL) receptor gene (LDL-R).

Lipoproteins abnormalities in obese insulin-resistant dogs.

Many studies have shown that obesity and low insulin sensitivity are associated with lipoprotein abnormalities, which are risk factors for coronary heart disease. The effects of insulin resistance on lipoprotein metabolism were investigated in hyperenergetic-fed beagle dogs, a new model of insulin resistance. Insulin resistance was assessed by the 3-hour euglycemic-hyperinsulinemic glucose clamp technique.

Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes.

Seven hypertriglyceridemic patients with type-2 diabetes were treated with atorvastatin (40 mg/day) for 2 months. Kinetics of apolipoprotein B100 (apoB100)-containing lipoproteins were determined before and after atorvastatin treatment and compared with data obtained in five normolipidemic volunteers. ApoB100 metabolism was studied using stable isotopes and multicompartmental modeling.