Cholecystectomy increases hepatic triglyceride content and very‐low‐density lipoproteins production in mice

Amigo, Ludwig; Husche, Constanze; Zanlungo, Silvana; Lütjohann, Dieter; Arrese, Marco; Miquel, Juan Francisco; Rigotti, Attilio; Nervi, Flavio

doi:10.1111/j.1478-3231.2010.02361.x

Cited by 72 publications

(59 citation statements)

References 77 publications

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“…Sonne et al ( 33 ) recently demonstrated a slight deterioration of postprandial glycemic control aft er GB removal, and even an increase in body weight has been reported in cholecystectomized patients ( 34 ). Moreover, and in line with current data from Ruhl and Everhard, recent studies in cholecystectomized mice have shown an increase in hepatic and serum TGs concentration, very-low-density lipoprotein synthesis and production, and BA pool cycling ( 35 ).…”

mentioning

confidence: 76%

Editorial : Cholecystectomy and NAFLD: Does Gallbladder Removal Have Metabolic Consequences?

Nervi

Arrese

2013

American Journal of Gastroenterology

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Pathogenesis of nonalcoholic fatty liver (NAFLD) disease and gallbladder (GB) disease secondary to cholesterol gallstones is complex, yet both conditions share similar associated risk factors, most of them related to the metabolic syndrome. Cholecystectomy, the best treatment for GB disease, is one of the most performed abdominal surgeries worldwide. In this issue of the American Journal of Gastroenterology , Ruhl and Everhart, using data from the Third United States National Health and Nutrition Examination Survey (1988 -1994), show that NAFLD is associated with cholecystectomy (odds ratio (OR) = 2.4; 1.8 -3.3), but not with gallstones (OR = 1.1; 0.84 -1.4). This fi nding suggests that cholecystectomy may itself represent a risk factor for NAFLD, which is in line with the recently undisclosed role of the GB and bile acids in systemic metabolic regulation. Thus, cholecystectomy may not be innocuous and may have a major impact on public health by contributing to NAFLD development.

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mentioning

confidence: 76%

Editorial : Cholecystectomy and NAFLD: Does Gallbladder Removal Have Metabolic Consequences?

Nervi

Arrese

2013

American Journal of Gastroenterology

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“…Following surgery, the size of the BA pool remains within a normal range and dietary fat absorption remains unaffected. 4,5 However, there is emerging evidence showing that cholecystectomy itself may lead to an excessive risk for the surgical patient developing metabolic disorders and their associated complications, including dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and hyperglycemia. [5][6][7] The unexplained high incidence of these metabolic abnormalities among cholecystectomized patients, combined with the lack of data regarding metabolic changes that occur after GB removal, has caused cholecystectomies to receive increased scrutiny.…”

mentioning

confidence: 99%

“…4,5 However, there is emerging evidence showing that cholecystectomy itself may lead to an excessive risk for the surgical patient developing metabolic disorders and their associated complications, including dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and hyperglycemia. [5][6][7] The unexplained high incidence of these metabolic abnormalities among cholecystectomized patients, combined with the lack of data regarding metabolic changes that occur after GB removal, has caused cholecystectomies to receive increased scrutiny. As the roles of the GB and BAs in systemic metabolic regulation have become better understood, [8][9][10] it is important to re-examine the potential long-term negative outcomes of GB removal, and especially the associated risk for subsequent metabolic syndrome (MetS).…”

mentioning

confidence: 99%

Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms

Chen

Tian

2018

Laboratory Investigation

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Cholecystectomy has long been regarded as a safe procedure with no deleterious influence on the body. However, recent studies provide clues that link cholecystectomy to a high risk for metabolic syndrome (MetS). In the present review, we describe the epidemiologic evidence that links cholecystectomy to MetS. Various components of MetS are investigated, including visceral obesity, dyslipidemia, elevated blood pressure, impaired fasting glucose, and insulin resistance. The possible mechanisms that associate cholecystectomy with MetS are discussed on the basis of experimental studies.

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“…In sham-operated control mice, the peritoneal cavity was opened and exposed, but the cystic duct was neither ligated nor removed [32] . After ensuring that the mice continued to gain weight nor-mally, we orally administered DHP107 to the sham-operated and cholecystectomized mice at a dose of 50 mg/kg under fasted conditions (n=5/time point).…”

Section: Cholecystectomy and Sampling In Micementioning

confidence: 99%

Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a hydrated lipidic sponge phase

et al. 2016

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Paclitaxel is a most widely used anticancer drug with low oral bioavailability, thus it is currently administered via intravenous infusion. DHP107 is a lipid-based paclitaxel formulation that can be administered as an oral solution. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of DHP107 in mice and rats by changing the dosing interval, and evaluated the influence of bile excretion. DHP107 was orally administered to mice at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107 affected paclitaxel absorption during subsequent administration. Studies with small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The AUC values after the second dose were smaller than those after the first dose, which was correlated to the induction of expression of P-gp and CYP in the livers and small intestines from 2 h to 7 d after the first dose. The smaller AUC value observed after the second dose was also attributed to the intestinal adhesion of residual formulation. The adhered DHP107 may have been removed by ingested food, thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the formulation adhered to the villi for up to 24 h, and the amount of DHP107 that adhered was approximately half that of monoolein. The paclitaxel absorption after administration of DHP107 was not affected by bile in the cholecystectomy mice. The dosing interval and food intake affect the oral absorption of paclitaxel from DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion does not affect the absorption of paclitaxel from DHP107 in vivo.

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Cholecystectomy increases hepatic triglyceride content and very‐low‐density lipoproteins production in mice

Cited by 72 publications

References 77 publications

Editorial : Cholecystectomy and NAFLD: Does Gallbladder Removal Have Metabolic Consequences?

Editorial : Cholecystectomy and NAFLD: Does Gallbladder Removal Have Metabolic Consequences?

Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms

Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a hydrated lipidic sponge phase

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