Browsing by Author "Quinones, V"

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    Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice
    (LIPID RESEARCH INC, 2001) Mardones, P; Quinones, V; Amigo, L; Moreno, M; Miquel, JF; Schwarz, M; Miettinen, HE; Trigatti, B; Krieger, M; VanPatten, S; Cohen, DE; Rigotti, A
    The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in cholesterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) cholesterol metabolism, intestinal SR-BI has been proposed to facilitate cholesterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of cholesterol and bile salts, we studied biliary lipid secretion, hepatic sterol content and synthesis, bile acid metabolism, fecal neutral sterol excretion, and intestinal cholesterol absorption in SR-BI knockout mice. SR-BI deficiency selectively impaired biliary cholesterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified cholesterol contents were slightly increased in SR-BI-deficient mice, while sterol synthesis was not significantly changed, Bile acid pool size and composition, as well as fecal bile acid excretion, were not altered in SR-BI knockout mice. Intestinal cholesterol absorption was somewhat increased and fecal sterol excretion was slightly decreased in SR-BI knockout mice relative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL cholesterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal cholesterol absorption.
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    Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice
    (WILEY, 2002) Amigo, L; Mendoza, H; Castro, J; Quinones, V; Miquel, JF; Zanlungo, S
    Receptor-mediated endocytosis is one of the major mechanisms for uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component in the intracellular distribution of cholesterol obtained from lipoproteins by the endocytic pathway, it may play a critical role in controlling plasma lipoprotein cholesterol and its biliary secretion. A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (- / -)] mouse, was used to evaluate the relevance of hepatic NPC1 expression in regulating plasma lipoprotein cholesterol profile and biliary lipid secretion under chow and high-cholesterol diets. Total plasma cholesterol concentrations were increased in NPC1 (- / -) mice compared with wild-type mice when both mouse strains were fed chow or high-cholesterol diets. The increased plasma cholesterol levels found in NPC1 (- / -) mice were mostly due to elevated cholesterol content in larger and more heterogeneous HDL particles. On the chow diet, biliary lipid secretion was not impaired by NPC1 deficiency. Furthermore, chow-fed NPC1 (- / -) mice showed a small, but significant, increase in biliary cholesterol secretion. On the high-cholesterol diet, wild-type mice increased biliary cholesterol output, whereas NPC1 (- / -) mice did not. Finally, hepatic NPCI overexpression by adenovirus-mediated gene transfer increased biliary cholesterol secretion by 100% to 150% in both wild-type mice and cholesterol-fed NPC1 (- / -) mice. In conclusion, hepatic NPC1 expression is an important factor for regulating plasma HDL cholesterol levels and biliary cholesterol secretion in mice.
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    Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice
    (W B SAUNDERS CO, 2000) Zanlungo, S; Amigo, L; Mendoza, H; Miquel, JF; Vio, C; Glick, JM; Rodriguez, A; Kozarsky, K; Quinones, V; Rigotti, A; Nervi, F
    Background & Aims: Sterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo. Methods: Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice. Results: SCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed. Conclusions: These results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism and intestinal cholesterol absorption.