Plasma Lipid Profiles of Transgenic mice expressing the Human ApoB100XCETP are altered differentially by Diets enriched with defined Fatty Acids

Abstract

Dietary fat is known to modulate plasma lipid profiles. Synthesis of high density lipoproteins (HDL), which has protective effects on vascular disease is also influenced by dietary fats, but the mechanisms are unclear. The hapoB100XCETP transgenic mouse was used to investigate the effects of fatty acids on the metabolism of plasma lipoproteins, including the pathway leading to synthesis HDL. Male transgenic mice were fed with diets formulated to provide TG (33% energy) as tripalmitin (TP), triolein (TO), tristearin (TS) or equicaloric substitution of fat with carbohydrate (sucrose) for 4 weeks. Analysis of plasma profile showed that HDL-cholesterol were 53.7+14; 64.6+8.6; 50.2+3.3; 47.0+9.2 and 45.2+4.9 mg/dL for control, oleate, palmitate, stearate and sucrose based diets, respectively. LDL-cholesterol levels were 51.7+7.0; 23.1+7.0; 38.9+2.2; 75.1+1.8 and 46.8.1.0 mg/dl, for control, TO, TP, TS and sucrose, respectively. Hepatic Lecithin-cholesterol acyltransferase (LCAT) protein levels increased by 2-fold in mice fed TS or TO diets, compared to TP, while sucrose had no effect. The scavenger receptor class B type I (SR-B1) which plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues increased in livers of animals fed TP and TO, while TS and sucrose did not have a similar effects. These results suggests that fatty acids can uniquely impact HDL, in addition, the ApoB100XCETP mouse is a useful model for the evaluation of how dietary components affect the risk of developing atherosclerosis and heart disease.

Impact of Dietary Lipids on the Reverse Cholesterol Transport: What We Learned from Animal Studies

“…Interestingly, the plasma activities of the main HDL-remodeling enzymes, CETP and LCAT, were not affected by the ingestion of a diet that was highly enriched in SFA (16.5% w/w , mainly from coconut oil or butter) when compared with hamsters fed with another high fat diet (16.5% w/w ), whereas PLTP activity was significantly higher in hamsters fed with coconut oil [ 152 ]. Consistently, a regular chow diet enriched with palmitic acid (15% w/w ) did not affect hepatic LCAT expression and mass in mice expressing both human CETP and apoB100, although the main liver HDL receptor, SR-BI, was upregulated [ 153 ]. CETP activity was not affected by dietary SFA either (when changed from 5% to 20% w/w ) in human CETP transgenic mice [ 154 ].…”

“…However, the ingestion of a diet that was highly enriched in MUFA (mainly from canola oil, 10% w/w ) did not affect LCAT, PLTP, or CETP activities in hamsters when compared with the animals fed with other high fat diets [ 152 ]. A regular chow diet enriched with oleic acid (providing 27% of the total calories from fat) also upregulated hepatic LCAT expression and mass, as well as SR-BI expression in human CETP and apoB100 transgenic mice [ 153 ]. Furthermore, dietary MUFA (12.6 % w/w of total fats) downregulated CETP expression and mass in the liver of human CETP transgenic mice [ 154 ].…”