Browsing by Author "Luetjohann, Dieter"

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    Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice
    (WILEY, 2011) Amigo, Ludwig; Husche, Constanze; Zanlungo, Silvana; Luetjohann, Dieter; Arrese, Marco; Miquel, Juan F.; Rigotti, Attilio; Nervi, Flavio
    Background & aims: Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism. Methods: Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined. Results: BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P < 0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P < 0.03) and 50% (P < 0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P < 0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice. Conclusions: XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver.
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    Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease
    (WILEY-BLACKWELL, 2012) Krawczyk, Marcin; Luetjohann, Dieter; Schirin Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Francisco Miquel, Juan
    In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Conclusion: Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. (HEPATOLOGY 2012)