Serum bile acid level and fatty acid composition in Chinese children with non‐alcoholic fatty liver disease

Lu, Li Ping; Yan, Wei; Xun, Pengcheng; Zhou, Ke; Chen, Cheng; Cheng, Si; Zhang, Min Zhong; Wu, Chun; Wang, Lin; Jiang, Ying; Feng, Hai; Wang, Jia Lu; He, Ka; Cai, Wei

doi:10.1111/1751-2980.12494

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…This is supported by studies in Chinese children were levels of chenodeoxycholic acid (CDCA) were increased in the moderate/severe stage of NAFLD. The authors report, that decreased circulating level of deoxycholic acid (DCA) in children with mild NAFLD might have a negative effect on the activation of FXR, which subsequently triggers an increasing production of CDCA in patients with moderate to severe NAFLD [ 45 ]. In contrast, Jiao and colleagues [ 39 ] found increased DCA and decreased CDCA levels in NAFLD patients.…”

Section: Discussionmentioning

confidence: 99%

Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial

2018

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients.MethodsFor this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28.3 kg/m2), 12 obese (35.3 kg/m2) and 16 healthy controls (24.2 kg/m2). All individuals received 1 g fat (Calogen®) per kg body weight orally. Serum concentrations of FGF19 were determined by ELISA. Concentrations of BAs and BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively; all at 0 (baseline), 2, 4 and 6 h during the OFTT.ResultsBMI correlated negatively with fasting FGF19 concentrations (rho = − 0.439, p = 0.004). FGF19 levels of obese NAFLD patients were significantly (p = 0.01) lower in the fasting state (median 116.0 vs. 178.5 pg/ml), whereas overweight NAFLD patients had significantly (p = 0.004) lower FGF19 concentrations 2 h after the fat load (median 163.0 vs. 244.5 pg/ml), and lowest values at all postprandial time points as compared to controls. Baseline BA concentrations correlated positively with FGF19 values (rho = 0.306, p = 0.048). In all groups, we observed BA increases during the OFTT with a peak at 2 h but no change in C4 levels in overweight/obese NAFLD patients.ConclusionsReduced basal gastrointestinal FGF19 secretion and decreased postprandial response to oral fat together with blunted effect on BA synthesis indicate alterations in intestinal or hepatic FXR signaling in overweight and obese NAFLD subjects. The precise mechanism of FGF19 signaling after oral fat load needs further evaluation.Trial registrationWe have registered the trial retrospectively on 30 Jan 2018 at the German clinical trials register (http://www.drks.de/), and the following number has been assigned DRKS00013942.Electronic supplementary materialThe online version of this article (10.1186/s12876-018-0805-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial

2018

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“…In a most recent third study with 35 control children at ages 12.8 ± 4.2 and 41 NAFLD children at ages 13.7 ± 2.4, which were further divided into mild and moderate/severe NAFLD groups, no significant alternations in serum total, primary, and secondary bile acids were detected in children with NAFLD compared to control subjects [103]. Most of individual bile acid species (CA, CDCA, DCA, and LCA), conjugated and unconjugated bile acids, were comparable among the groups.…”

Section: Serum Bile Acid Profiling In Children With Nafldmentioning

confidence: 94%

“…Bile acid alterations gets worsening in patients with advanced stages of NAFLD, such as NASH, compared to the patients with simple steatosis [86,88,101,102,107]. Some studies differentiate NAFLD patients into simple steatosis and NASH [86,88,101,102,107], while the others [38,87,89,91,103] do not, which certainly influences the outcomes of the studies. Third, NAFLD is often associated with various metabolic conditions, especially obesity and insulin resistance/diabetes.…”

Section: Fecal and Urine Bile Acidsmentioning

confidence: 99%

Dysregulation of Bile Acids in Patients with NAFLD

Zhang¹,

Deng²

2019

Nonalcoholic Fatty Liver Disease - An Update

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Bile acids are synthesized in the liver and tightly regulated through the enterohepatic circulation. Recent studies reveal that bile acids serve as hormone-like signaling molecules to activate nuclear receptors, notably farnesoid X receptor (FXR), regulating metabolic homeostasis of bile acids, cholesterol, lipids, and glucose. A connection between bile acids and nonalcoholic fatty liver disease (NAFLD) has long been recognized. Although inconsistent or even contradictory results are reported, a large body of evidence from clinical as well as preclinical studies demonstrates that bile acid homeostasis is disrupted in patients with NAFLD. The bile acid dysregulation gets worsening as NAFLD progresses from early stage simple steatosis to late stage nonalcoholic steatohepatitis (NASH) and NASH with fibrosis. As the risk factors for NAFLD, obesity and insulin resistance, which are often associated with NAFLD, contribute to the dysregulation of bile acids in patients with NAFLD. Total serum and fecal bile acid concentrations are mostly elevated in patients with NAFLD as a result of increased bile acid synthesis, elevated hepatic bile acids, and upregulation of bile acid transporters. The two negative feedback regulatory pathways for bile acid synthesis, FXR/SHP (small heterodimer partner) and fibroblast growth factor-19 (FGF19)/FGF receptor-4 (FGFR4), are impaired in patients with NAFLD.

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“…In children with NAFLD, changes in circulating BA profile have been reported too [39, 69]. The research of Jahnel et al demonstrates that serum BA levels decrease in early NAFLD and increase during progression to fibrosis in obese children.…”

Section: Gut Microbiota-derived Mediators In Nafldmentioning

confidence: 99%

Gut Microbiota-Derived Mediators as Potential Markers in Nonalcoholic Fatty Liver Disease

Aragonès

González-García

Aguilar

et al. 2019

BioMed Research International

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Nonalcoholic fatty liver disease (NAFLD) is a common, multifactorial, and poorly understood liver disease whose incidence is globally rising. During the past decade, several lines of evidence suggest that dysbiosis of intestinal microbiome represents an important factor contributing to NAFLD occurrence and its progression into NASH. The mechanisms that associate dysbiosis with NAFLD include changes in microbiota-derived mediators, deregulation of the gut endothelial barrier, translocation of mediators of dysbiosis, and hepatic inflammation. Changes in short chain fatty acids, bile acids, bacterial components, choline, and ethanol are the result of altered intestinal microbiota. We perform a narrative review of the previously published evidence and discuss the use of gut microbiota-derived mediators as potential markers in NAFLD.

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Serum bile acid level and fatty acid composition in Chinese children with non‐alcoholic fatty liver disease

Abstract: Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action.

Cited by 19 publications

References 28 publications

Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial

Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial

Dysregulation of Bile Acids in Patients with NAFLD

Gut Microbiota-Derived Mediators as Potential Markers in Nonalcoholic Fatty Liver Disease

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