Browsing by Author "Moreno, M"

Now showing 1 - 3 of 3
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    Expression and regulation of scavenger receptor class B type I (SR-BI) in gall bladder epithelium
    (BMJ PUBLISHING GROUP, 2003) Miquel, JF; Moreno, M; Amigo, L; Molina, H; Mardones, P; Wistuba, II; Rigotti, A
    Background and aims: Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR-BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation.
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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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    Hepatic overexpression of caveolins increases bile salt secretion in mice
    (WILEY, 2003) Moreno, M; Molina, H; Amigo, L; Zanlungo, S; Arrese, M; Rigotti, A; Miquel, JF
    Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2-infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a significant increase in plasma high-density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav-1 overexpression. No changes were seen in the protein mass of BS transporters NtcP and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.