ArticleThe Journal of biological chemistry2011
Disruption of the murine protein kinase Cbeta gene promotes gallstone formation and alters biliary lipid and hepatic cholesterol metabolism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Hepatic protein kinase Cβ antagonizing p38American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Sphincter of Oddi Dysfunction Induces Gallstone by Inhibiting the Expression of ABCB11 via PKC-α.Applied biochemistry and biotechnology · 2024Article
- A protein kinase C α and β inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.Scientific reports · 2023Article
- Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids in health and disease · 2020Review
- Mouse models of gallstone disease.Current opinion in gastroenterology · 2018Review
- Dietary fat/cholesterol-sensitive PKCβ-RB signaling: Potential role in NASH/HCC axis.Oncotarget · 2017Article
- PKCβ: Expanding role in hepatic adaptation of cholesterol homeostasis to dietary fat/cholesterol.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Modulation of Hepatic Protein Kinase Cβ Expression in Metabolic Adaptation to a Lithogenic Diet.Cellular and molecular gastroenterology and hepatology · 2015Article
- Metabolic syndrome and gallstone disease.World journal of gastroenterology · 2012Article
- Delineation of biochemical, molecular, and physiological changes accompanying bile acid pool size restoration in Cyp7a1(-/-) mice fed low levels of cholic acid.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
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 Cβ (PKCβ), a calcium-, diacylglycerol-, and phospholipid-dependent kinase, is critical for maintaining whole body triglyceride 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-7α-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 of 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.
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