| Disruption of the murine protein kinase C{beta} gene promotes gallstone formation and alters biliary lipid and hepatic cholesterol metabolism. | |
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MedLine Citation:
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PMID: 21550971 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The protein kinase C (PKC) family of Ca(2+) and/or lipid-activated serine-threonine protein kinases is implicated in the pathogenesis of obesity and insulin resistance. We recently reported that protein kinase C beta (PKCβ) a calcium, diacylglycerol- and phospholipid-dependent kinase,is critical for maintaining whole-body TG homeostasis. We now report that PKCβ deficiency has profound effects on murine hepatic cholesterol metabolism, including hypersensitivity to diet-induced gallstone formation. The incidence of gallstones increased from 9% in control mice to 95% in PKCβ(-/-) mice. Gallstone formation in the mutant mice was accompanied by hyposecretion of bile acids with no alteration in fecal bile acid excretion, increased biliary cholesterol saturation and hydrophobicity indices, as well as hepatic p42/44 (MAPK+) activation,all of which enhance susceptibility to gallstone formation. Lithogenic diet fed PKCβ(-/-) mice also displayed decreased expression of hepatic cholesterol-7 α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8b1). Finally, feeding a modified lithogenic diet supplemented with milk fat, instead of cocoa butter, both increased the severity and shortened the interval for gallstone formation in PKCβ(-/-) mice and was associated with dramatic increases in cholesterol saturation and hydrophobicity indices. Taken together, the findings reveal a hitherto unrecognized role of PKCβ in fine tuning diet-induced cholesterol and bile acid homeostasis, thus identifying PKCβ as a major physiological regulator of both triglyceride and cholesterol homeostasis.p> |
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Authors:
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Wei Huang; Rishipal R Bansode; Yan Xie; Leslie Rowland; Madhu Mehta; Nicholas O Davidson; Kamal D Mehta |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-5 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Ohio State University College of Medicine, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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