Apoprotein E biosynthesis in the cholesterol-fed guinea pig.

Abstract

Apoprotein E biosynthesis was evaluated In the livers of guinea pigs fed chow, 1% cholesterol plus 5% corn oil, or 1% cholesterol plus 5% coconut oil for a period of 12 weeks. Hypercholesterolemla was Induced by both experimental diets, although the coconut-oil diet resulted in higher levels. The ratios of free cholesterol/ cholesterol ester and of free cholesterol/total phosphollpid increased In the plasma of these animals. Peak lipid levels were mostly achieved by 8 weeks of diet Both cholesterol and triglyceride were substantially increased In the liver of animals fed the experimental diets, while phospholipid content was unchanged. The amount of apoprotein E mRNA In the guinea pig livers was evaluated by cell free translation assays and by membrane hybridization. The livers of animals fed corn oil with cholesterol for 4 weeks or 8 weeks contained 2 to 2.5 more apoprotein E mRNA compared to the control livers. With the diet containing coconut oil with cholesterol, the hepatic apoprotein E mRNA Increased somewhat later, so that by 8 weeks It was 1.7-to 1.9-fold higher than in the control animals. We conclude that high cholesterol diets, when fed as part of a high saturated or polyunsaturated fat diet, lead to Increased hepatic apo E mRNA abundance. The relationship between the Increased apo E mRNA levels and the previously described Increases in apo E synthesis and circulating apo E levels Is discussed. (Arteriosclerosis 10:31-39, January/February 1990)A polipoprotein E (apo E) is a 35 000 dalton glycoprctein found in many classes of mammalian plasma lipoproteins.1 Apo E is important in the metabolism of cholesterol-ester rich lipoproteins by virtue of its interaction with at least two lipoprotein receptor systems, the LDL receptor and the chylomicron remnant receptor.23 Plasma levels of apo E increase in a variety of circumstances, including diabetes, hypothyroidism, and cholesterol feeding. 46 In several species, cholesterol feeding leads to the appearance of new lipoproteins, /3-VLDL and HDLc, both of which are rich in cholesterol ester and epo E. The guinea pig has an unusual response to cholesterol feeding. In the normal guinea pig, the bulk of the plasma cholesterol is carried by low density lipoprotein (LDL), with high density lipoprotein (HDL) transporting less than 5% of the total cholesterol. 67 When guinea pigs are fed a diet supplemented with 1% cholesterol and 5% com or cottonseed oil, their plasma cholesterol levels increase from less than 100 mg/dl to 300 mg/dl within 10 days.68 Dietary

Effect of Honey Bee on Some Antioxidant Enzymes and Lipid Profile in Hypercholesterolemic Male Albino Rats

“…Increased VLDL-C level significantly may be due to that the oil increased lipoprotein synthesis in liver and VLDL, the major lipoprotein synthesized. These results agreed with Driscoll et al (52) and Fungwe et al (53) who reported increases in plasma TG and hepatic lipid in ginea pigs fed cholesterol in chow diets containing corn or coconut oil and in rabbits received coconut oil. Increased VLDL-C may be attributed to decreased lipoprotein lipase activity (54) .…”

AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity

“…In this regard, transcription from the ApoE promoter has already been reported to be induced in the liver after high-fat and/or high-cholesterol feeding in different spe-cies, including mice, rat, guinea pig, rabbit, and cow. [24][25][26][27][28] In agreement, the lean-chow-fed animals at 4 and 12 weeks after treatment with AAV-BMP7 showed circulating levels much lower than HFD-fed AAV-BMP7-treated mice (Figure 1C). As body and liver weight normalized, serum BMP7 concentration also decreased in HFD-fed AAV-BMP7treated mice, reaching levels similar to those of chow-fed AAV-BMP7-treated mice at the end of the study (Figure 1C).…”

LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL

“…Previous in vivo studies utilizing guinea pig [8] and cebus monkey [9] have shown that cholesterol feeding to these animals resulted in the up-regulation of apoE gene in the liver, raising the possibility that the accumulation of cholesterol in hepatocytes would affect hepatic up-regulation of the apoE gene. In addition, investigation in mice also indicated the up-regulation of hepatic apoE gene by cholesterol feeding [10].…”