Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster

Abstract

Diets rich in polyunsaturated fatty acids lower plasma HDL cholesterol concentrations when compared to diets rich in saturated fatty acids. We investigated the mechanistic basis for this effect in the hamster and sought to determine whether reduced plasma HDL cholesterol concentrations resulting from a high polyunsaturated fat diet are associated with a decrease in reverse cholesterol transport. Animals were fed semisynthetic diets enriched with polyunsaturated or saturated fatty acids for 6 weeks. We then determined the effect of these diets on the following parameters: 1 ) hepatic scavenger receptor B1 (SR-BI) mRNA and protein levels, 2 ) the rate of hepatic HDL cholesteryl ester uptake, and 3 ) the rate of cholesterol acquisition by the extrahepatic tissues (from de novo synthesis, LDL and HDL) as a measure of the rate of reverse cholesterol transport. Compared to saturated fatty acids, dietary polyunsaturated fatty acids up-regulated hepatic SR-BI expression by ϳ 50% and increased HDL cholesteryl ester transport to the liver; as a consequence, plasma HDL cholesteryl ester concentrations were reduced. Although dietary polyunsaturated fatty acids increased hepatic HDL cholesteryl ester uptake and lowered plasma HDL cholesterol concentrations, there was no change in the cholesterol content or in the rate of cholesterol acquisition (via de novo synthesis and lipoprotein uptake) by the extrahepatic tissues. These studies indicate that substitution of polyunsaturated for saturated fatty acids in the diet increases SR-BI expression and lowers plasma HDL cholesteryl ester concentrations but does not affect reverse cholesterol transport. -Spady, D. K., D. M. Kearney, and H. H. Hobbs. Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster.

Cholesterol, bile acid, and lipoprotein metabolism in two strains of hamster, one resistant, the other sensitive (LPN) to sucrose-induced cholelithiasis

“…Much of the understanding of its physiological role has been deduced from genetic manipulations in mice, which produce spectacular alterations in plasma and biliary lipid parameters (50). Under more physiological conditions in hamsters, an inverse relationship between HDL cholesterol level and hepatic SR-BI expression has been reported (51), but other results are consistent with no association ( 52), as found in the present study. We observed only minor changes in SR-BI or LDL receptor levels in the face of increased plasma HDL and LDL cholesterol concentrations for both strains of hamsters when challenged for the sucrose-rich diet.…”

Sources of eicosanoid precursor fatty acid pools in tissues

“…The SR-BI in adrenal gland is upregulated in HL knockout mice (152), and acute in vivo inhibition of HL activity increased rat adrenal SR-BI expression and uptake of HDL-CE (153). Substitution of PUFA in the diet of hamsters increases SR-BI expression and lowers plasma HDL-CE concentrations (154), indicating that PUFA in the diet in addition to steroids and hypophyseal hormones (155) may regulate the SR-BI. Because in contrast HL is upregulated by EFA deficiency this further support the reciprocal regulation and the complementary action of HL and the SR-BI in the transport of PUFA.…”

Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine

“…However, pharmacological doses of estrogen or chronic feeding of rats with a cholesterol-enriched diet has been shown to reduce SR-BI expression in hepatocytes while inducing its expression in the Kupffer cells (8,10). In hamsters, hepatic expression of SR-BI is resistant to dietary cholesterol feeding, but can be induced by a PUFA-enriched diet (11,12). Both estrogen-and diet-induced hepatic SR-BI expression correlate positively with increased HDL cholesteryl ester transport to the liver and reduction of plasma HDL cholesterol concentration (8,11).…”

“…In hamsters, hepatic expression of SR-BI is resistant to dietary cholesterol feeding, but can be induced by a PUFA-enriched diet (11,12). Both estrogen-and diet-induced hepatic SR-BI expression correlate positively with increased HDL cholesteryl ester transport to the liver and reduction of plasma HDL cholesterol concentration (8,11). A physiological role of hepatic SR-BI in mediating uptake of HDL-associated neutral lipids was demonstrated in genetically modified animals.…”