References
Query Results -- Details
MGI Accession ID: MGI:3606993
J Number: J:102144
Other Accession IDs:
Title: Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background impairs very-low-density lipoprotein production.
Authors: Post SM; Groenendijk M; Solaas K; Rensen PC; Princen HM
Journal: Arterioscler Thromb Vasc Biol
Volume: 24
Issue: 4
Date: 2004 Apr
Year: 2004
Pages: 768-74
Review Status: Peer Reviewed
Abstract:
OBJECTIVE: Cholesterol 7alpha-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. METHODS AND RESULTS: Female mice received a chow or lipogenic diet. On both diets, fecal bile acid excretion was 70% decreased concomitantly with a 2-fold increased neutral sterol output. The differences in bile acid biosynthesis did not change plasma cholesterol levels. However, plasma triglyceride levels decreased by 41% and 38% in the cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3-Leiden mice on chow and lipogenic diet, respectively. Mechanistic studies showed that very-low-density lipoprotein (VLDL)-apolipoprotein B and VLDL-triglyceride production rates were reduced in cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3-Leiden mice (-34% and -35%, respectively). Cyp7a1 deficiency also increased the hepatic cholesteryl ester and triglyceride content (2.8-fold and 2.5-fold, respectively). In addition, hepatic anti-oxidative vitamin content, which can influence VLDL-production, was lower. Hepatic mRNA analysis showed decreased expression of genes involved in lipogenesis including srebf1. CONCLUSIONS: Cyp7a1 deficiency in APOE*3-Leiden mice decreases the VLDL particle production rate, as a consequence of a strongly reduced bile acid biosynthesis, leading to a decrease in plasma triglycerides. These data underscore the close relationship between bile acid biosynthesis and triglyceride levels.
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