title: Scavenger Receptor Class B Type I Regulates Plasma Apolipoprotein E Levels and Dietary Lipid Deposition to the Liver.
abstract: Scavenger receptor class B type I (SR-BI) is primarily responsible for the selective uptake of cholesteryl esters (CE) of high-density lipoprotein (HDL) by the liver and other tissues. In the present study, we show that SR-BI-deficient (scarb1(-/-)) mice are resistant to diet-induced obesity, hepatic lipid deposition, and glucose intolerance after 24 weeks of being fed a western-type diet. No differences in energy expenditure or mitochondrial function could account for the observed phenotype. Kinetic and gene expression analyses suggested reduced de novo fatty acid synthesis in scarb1(-/-) mice. Furthermore, adenosine monophosphate-activated protein kinase (AMPK)-stimulated hepatic FFA catabolism was reduced in these mice, leaving direct dietary lipid uptake from plasma as the major modulator of hepatic lipid content. Analysis of the apolipoprotein composition of plasma lipoproteins revealed a significant accumulation of apolipoprotein E (ApoE)-containing HDL and TG-rich lipoproteins in scarb1(-/-) mice that correlated with reduced plasma LpL activity. Our data suggest that scarb1(-/-) mice fed a western-type diet for 24 weeks accumulate CE- and ApoE-rich HDL of abnormal density and size. The elevated HDL-ApoE levels inhibit plasma LpL activity, blocking the clearance of triglyceride-rich lipoproteins and preventing the shuttling of dietary lipids to the liver.
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Eleni A
authors: EA
authors: Karavia
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Nikolaos I
authors: NI
authors: Papachristou
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: George C
authors: GC
authors: Sakellaropoulos
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Eva
authors: E
authors: Xepapadaki
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Eleni
authors: E
authors: Papamichail
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Peristera-Ioanna
authors: PI
authors: Petropoulou
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Eugenia P
authors: EP
authors: Papakosta
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Caterina
authors: C
authors: Constantinou
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Ioannis
authors: I
authors: Habeos
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Dionysios J
authors: DJ
authors: Papachristou
authors: Pharmacology Department, ‡Anatomy Histology and Embryology Department, §Medical Physics Department, and ∥Endocrinology Department, University of Patras Medical School , Rio Achaias, TK 26500, Greece.
authors: Kyriakos E
authors: KE
authors: Kypreos
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood*; D004041:Dietary Fats / Q000378:metabolism*; D004734:Energy Metabolism; D008071:Lipoprotein Lipase / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D008071:Lipoprotein Lipase