Papers by Folkert Kuipers
Trends in Endocrinology and Metabolism, Feb 1, 2018
Biochemical Journal, Feb 15, 1991
Journal of Hepatology, Nov 1, 2002
Expression of hepatic bile salt transporters is partly regulated by bile salts via activation of ... more Expression of hepatic bile salt transporters is partly regulated by bile salts via activation of nuclear farnesoid X-activated receptor (Fxr). We investigated the physiological relevance of this regulation by evaluating transporter expression in mice experiencing different transhepatic bile salt fluxes. Bile salt flux was manipulated by dietary supplementation with taurocholate (0.5% w/w) or cholestyramine (2% w/w) or by disruption of the cholesterol 7alpha-hydroxylase-gene (Cyp7A(-/-) mice) leading to reduced bile salt pool size. Expression of hepatic transporters was assessed (polymerase chain reaction (PCR), immunoblotting, and immunohistochemistry). Biliary bile salt secretion was increased (+350%) or decreased (-50%) after taurocholate or cholestyramine feeding, respectively, but plasma bile salt concentrations and hepatic Fxr expression were not affected. The bile salt uptake system Na(+)-taurocholate co-transporting polypeptide (Ntcp) and organic anion transporting polypeptide-1 (Oatp1) were down-regulated by taurocholate and not affected by cholestyramine feeding. Cyp7A(-/-) mice did not show altered Ntcp or Oatp1 expression. Canalicular bile salt export pump (Bsep) was up-regulated by 65% in taurocholate-fed mice, and slightly down-regulated in Cyp7A(-/-) mice. Large variations in hepatic bile salt flux have minor effects on expression of murine Ntcp and Bsep in vivo, suggesting that these transporters are abundantly expressed and able to accommodate a wide range of 'physiological' bile salt fluxes.
Journal of Hepatology, 2009
Journal of Clinical Investigation, Dec 1, 1997
Circulation, Oct 25, 2005
Atherosclerosis Supplements, Jun 1, 2010
Chemistry and Physics of Lipids, Aug 1, 2008
The FASEB Journal, Apr 1, 2018
British Journal of Nutrition, Jul 3, 2020
Arteriosclerosis, Thrombosis, and Vascular Biology, Apr 1, 2017
European Journal of Pediatrics, Oct 1, 2002
Atherosclerosis, Oct 1, 2011
Objective: Regular physical activity decreases the risk for atherosclerosis but underlying mechan... more Objective: Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. Methods: Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. Results: RUN weighed less (∼13%) while food consumption was increased by 17% (p = 0.004). Plasma cholesterol levels were decreased by 12% (p = 0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p = 0.007) and increased fecal bile acid (93%, p = 0.009) and neutral sterol (33%, p = 0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p = 0.033). Conclusion: Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice.
Atherosclerosis, Aug 1, 2022
Diabetologia, Sep 1, 2006
Pediatric Research, Apr 1, 2003
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Papers by Folkert Kuipers