Dataset Information

Correlation between cholecystectomy and development of non-alcoholic liver disease in the mouse model.

ABSTRACT:

Background

Several clinical studies have suggested a strong correlation between cholecystectomy and the incidence of non-alcoholic fatty liver disease (NAFLD) although the exact correlation and causal relationship are unclear. This study aimed to investigate whether cholecystectomy increases the incidence of NAFLD or aggravates pre-existing NAFLD.

Methods

Standard diet-fed and high-fat (HF) diet-fed mice were subjected to sham operation and cholecystectomy. In study 1, 20 standard diet-fed C57BL/6N mice were sacrificed at months 1, 2, and 4 post-surgery. Meanwhile, in study 2, 25 HF diet-induced NAFLD C57BL/6N mice were biopsied at months 2 and 3 post-surgery and sacrificed at month 6 post-surgery. The hepatic fatty acid and bile acid metabolic pathways and the hepatic bile composition were evaluated.

Results

The bodyweight and biochemical parameters (hepatic enzyme, triglyceride, and cholesterol levels) were not significantly different between the standard diet-fed sham and cholecystectomy groups. The NAFLD activity score and the levels of hepatocyte apoptosis markers (Krt18 expression and DNA fragmentation) and de novo lipid synthesis genes were not significantly different between the standard diet-fed sham and cholecystectomy groups. Cholecystectomy did not exacerbate hepatic steatosis, inflammation, and ballooning in the HF diet-fed mice. Hepatic bile acid composition was not markedly different in the sham and cholecystectomy groups fed on standard or HF diet. Cholecystectomy significantly downregulated Cyp7a1 and Cyp27a1 mRNA levels at months 1 and 4 post-surgery but did not affect the degree of steatosis and triglyceride levels. Analysis of bile acid metabolism revealed that taurine-conjugated bile acids were significantly downregulated in the standard diet-fed and high-fat diet-fed mice, but the histological and biochemical parameters were not markedly different.

Conclusions

Cholecystectomy did not increase the incidence of NAFLD in standard diet-fed mice. Additionally, NAFLD incidence was not significantly different between the HF diet-fed sham and cholecystectomy groups. Furthermore, the histological parameters were not markedly different between the sham and cholecystectomy groups fed on standard or HF diet. These findings suggest that cholecystectomy does not induce NAFLD.

SUBMITTER: Kim HY

PROVIDER: S-EPMC9403915 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Correlation between cholecystectomy and development of non-alcoholic liver disease in the mouse model.

Kim Hye Young HY Lee Sung Ryol SR Saeed Waqar Khalid WK Kim Hyun Sung HS Oh Ju Hee JH Koh Dong Hee DH Jun Dae Won DW

Annals of translational medicine 20220801 15

<h4>Background</h4>Several clinical studies have suggested a strong correlation between cholecystectomy and the incidence of non-alcoholic fatty liver disease (NAFLD) although the exact correlation and causal relationship are unclear. This study aimed to investigate whether cholecystectomy increases the incidence of NAFLD or aggravates pre-existing NAFLD.<h4>Methods</h4>Standard diet-fed and high-fat (HF) diet-fed mice were subjected to sham operation and cholecystectomy. In study 1, 20 standard ...[more]

PMID: 36034996

Similar Datasets

Project description:Background & aimsThe accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.MethodsWe generated TIRF (transgene-free Il2rg -/-/Rag2 -/-/Fah -/-) mice, populated their livers with human hepatocytes, and fed them a Western-type diet for 12 weeks.ResultsWithin the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis.ConclusionsThese NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis.Lay summaryFatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in humans with fatty liver. This novel humanised mouse system can be used to study human fatty liver disease.

Project description:Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3-HFD+pioglitazone; 4-HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on hepatic lipid metabolism.

Project description:IntroductionNon-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with liver fibrosis (LF) being a crucial pathological feature in the progression of NAFLD. Insulin resistance (IR) is believed to play an important role in the pathogenesis of NAFLD and the development of LF. This study aims to explore the relationship between various IR indicators and LF in patients with NAFLD.MethodsThis study utilized data from the National Health and Nutrition Examination Survey 2017-2020 cycles. Liver steatosis and fibrosis were assessed using liver ultrasound transient elastography. To assess the association between multiple IR indicators and LF, the study methodology included univariate and multivariate logistic regression, as well as restricted cubic spline (RCS) analysis. Subsequently, we used multivariate logistic regression to develop and validate a predictive model for LF, and evaluated the model's performance using the area under the curve (AUC) and calibration curve.ResultsA total of 904 patients were included in the final analysis. Among these NAFLD patients, 153 (16.92%) had LF. Compared to non-LF patients, LF patients had significantly higher body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), HbA1c, and fasting blood glucose (FBG) levels (all p < 0.05). Analysis of IR indicators showed that LF patients had significantly higher levels of TyG, TyG-WHtR, TyG-BMI, TyG-WC, TyG-GGT, METS-IR, and HOMA-IR (all p < 0.05). After adjusting for covariates, TyG-WHtR remained an independent risk factor (OR=2.69; 95% CI: 2.08-3.47), indicating a strong correlation with LF. The developed nomogram, incorporating AST, TyG, TyG-BMI, and diabetes, showed an AUC of 0.809 (95% CI: 0.771-0.847), indicating good predictive performance for LF in NAFLD patients.ConclusionsThis study confirms that a significant association between various IR and LF in NAFLD patients, and the developed nomogram provides a practical tool for early risk assessment. These findings underscore the clinical value of incorporating IR indices into routine practice to identify high-risk patients, enabling timely interventions to prevent fibrosis progression and improve outcomes.

Dataset Information

Correlation between cholecystectomy and development of non-alcoholic liver disease in the mouse model.

Background

Methods

Results

Conclusions

Publications

Correlation between cholecystectomy and development of non-alcoholic liver disease in the mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets