Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

Barrera, Francisco; Azócar, Lorena; Molina, Helia; Schalper, Kurt A.; Ocares, Marcia; Liberona, Jéssica; Villarroel, Luís; Pimentel, Fernando; Pérez-Ayuso, Rosa María; Nervi, Flavio; Groen, Albert K.; Miquel, Juan Francisco

doi:10.1016/s1665-2681(19)30766-5

Cited by 59 publications

(65 citation statements)

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“…FGF19 has direct systemic metabolic effects on lipid and carbohydrate metabolism [48, 49]. Of note, serum FGF19 levels decrease after XGB [50] and have been found decreased in patients with NAFLD [51, 52]. Thus, it could be hypothesized that dysregulation of FGF 19 after XGB may in part mediate the metabolic consequences of XGB observed in this study.…”

Section: Discussionmentioning

confidence: 78%

Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients: a pilot study

et al. 2017

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BackgroundNonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Experimental studies have shown that cholecystectomy (XGB) increases hepatic fat content in mice and appears associated to NAFLD in large retrospective population-based studies. The aim of this study was to prospectively assess the effects of XGB on hepatic fat content (HFC) and insulin resistance (IR) in non-obese, middle aged Hispanic subjects.MethodsTwenty-six gallstone patients undergoing elective XGB and 16 control subjects with normal livers and gallbladders at ultrasonography were prospectively followed 24 months for changes in HFC and IR. Clinical, biochemical determinations and hepatic imaging were performed at baseline and 24 months after surgery. MRI technique quantified HFC in four hepatic segments. IR was assessed by the Homeostasis Model Assessment (HOMA-IR) index.ResultsInitial body mass index (BMI) was 25.6 ± 0.4 and 24.3 ± 1.0 in the control and XGB groups of subjects, respectively. Serum insulin level increased from 8.1 ± 0.7 to 10.0 ± 1.9 (μU/ml) 24 months after surgery in XGB patients (p < 0.05); no significant changes were detected in control individuals. Median HOMA-IR index increased from 1.31 (interquartile range, 1.01-1.68) to 2.20 (interquartile range, 1.57 - 2.60) 24 months after XGB, (p < 0.003). Median HOMA-IR index of control subjects remained unchanged at the end of the study. Serum apoB concentration increased from 61.5 ± 3.4 to 79.0 ± 7.8 (μg/ml) in XGB patients (p < 0.03). Serum apoB levels remained within normal ranges in both periods of the study in control subjects. HFC significantly increased in 2 of the 4 segments 24 months after XGB: right posterior hepatic lobe (from 5.3 ± 0.2% to 6.0 ± 0.2%, p > 0.04) and right anterior hepatic lobe (from 5.8 ± 0.2% to 6.6 ± 0.3%, p < 0.02). The average HFC of the four hepatic segments studied slightly increased from 5.4 ± 0.2 to 5.8 ± 0.3 2 years after XGB (p < 0.03). No significant changes were found in HFC in the control subjects at the end of the study.ConclusionsElective XGB increases HFC, HOMA-IR index and serum apoB concentration. These results support the notion that XGB is a risk factor non-alcoholic fatty liver disease and other IR – associated disease conditions.

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Section: Discussionmentioning

confidence: 78%

Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients: a pilot study

et al. 2017

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“…Disrupted concentration, blunted transintestinal flow, and fast enterohepatic re-circulation of BAs acting as signaling molecules, 26 will ultimately interfere with gene expression of BAs/FXR, and BA/GPBAR-1 axes. 25 A missing gallbladder will also impoverish the circulating levels of FGF19, 27 and eliminate the gallbladder GPBAR-1. As reviewed by Chen et al 2 this is a condition which promotes the shift toward unstable systemic abnormalities at root of the metabolic syndrome.…”

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confidence: 99%

Cholecystectomy: a way forward and back to metabolic syndrome?

Garruti

Wang

Ciaula

et al. 2018

Laboratory Investigation

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The gallbladder provides rhythmic secretion of concentrated bile acids (BAs) during fasting and postprandially contributes to digestion of dietary lipids. In addition, BAs activate metabolic pathways governing gluco-lipid homeostasis and energy expenditure via the farnesoid X nuclear receptor (FXR), G protein-coupled BA receptor 1 (GPBAR-1), and fibroblast growth factor 19 (FGF19) in the liver, intestine, brown fat, and muscle. Cholecystectomy is standard treatment worldwide for symptomatic gallstone patients. As excellently reviewed by Chen et al, cholecystectomy may disrupt enterohepatic recycling of, and signaling by, BAs. Further studies are needed to investigate whether gallbladder removal is an independent risk factor for development of the metabolic syndrome.

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“…FGF19 is abundantly expressed in the GB 52 and circulating levels of FGF19 are decreased in patients with GSD. 53 Surprisingly, we found that FGF19 mRNA levels were approximately 250-fold higher in GB cholangiocytes compared with distal ileum and that GB bile contained approximately 23-fold higher FGF19 levels compared with the serum, 53 suggesting that FGF15/19 could exert actions in the luminal surface of the intestine, that remain to be described.…”

Section: Potential Roles Of the Gb On Glucose And Lipid Metabolism mentioning

confidence: 89%

“…FGF19 is abundantly expressed in the GB and circulating levels of FGF19 are decreased in patients with GSD . Surprisingly, we found that FGF19 mRNA levels were approximately 250‐fold higher in GB cholangiocytes compared with distal ileum and that GB bile contained approximately 23‐fold higher FGF19 levels compared with the serum, suggesting that FGF15/19 could exert actions in the luminal surface of the intestine, that remain to be described. Interestingly, administration of FGF19 increases energy expenditure and decreases hyperglycaemia in diabetic mice, possibly by activating brown adipose tissue‐dependent thermogenesis and decreasing hepatic gluconeogenesis, respectively, and cooperating with the metabolic actions of BA‐activated FXR during the post‐absorptive phase .…”

Section: Potential Roles Of the Gb On Glucose And Lipid Metabolism Anmentioning

confidence: 99%

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

2019

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Summary Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.

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Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

Cited by 59 publications

References 43 publications

Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients: a pilot study

Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients: a pilot study

Cholecystectomy: a way forward and back to metabolic syndrome?

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

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