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Purpose: Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM., Methods: Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions., Results: The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90-1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97-1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM., Conclusions: The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM., (© 2024. The Author(s).)

Background & Aims: How hepatic steatosis progresses to non-alcoholic steatohepatitis (NASH) is complicated and remains unclear. The mortality factor 4-like protein 1 (MORF4L1, also called MRG15) was previously identified as a master nuclear chromatin remodeler in the rhythmic regulation of lipid synthesis gene expression in the liver. Whether it also contributes to the progression from liver steatosis to NASH is unclear., Methods: We adopted 2 different murine NASH models, liver biopsies from patients with NASH, and primary mouse and human hepatocyte cultures for functional examination of MRG15 in NASH progression. Immunoprecipitation-mass spectrometry was applied to identify protein partners of MRG15, and CRISPR targeting was used for gene depletion in liver cells in vivo., Results: The MRG15 level is increased in the livers of humans and mice with NASH. The inflammatory cytokines in NASH livers stabilize MRG15 by increasing its acetylation. Considerable amounts of MRG15 associate with the outer mitochondrial membrane, where it interacts with and deacetylates the mitochondrial Tu translation elongation factor (TUFM). Deacetylated TUFM, especially at the K82 and K91 sites, is subjected to accelerated degradation by the mitochondrial ClpXP protease system. Reduced liver TUFM consequently results in impaired mitophagy, increased oxidative stress and activation of the NLRP3 inflammasome pathway. Blocking MRG15 expression protects the liver from NASH progression by increasing the stability of liver TUFM. Liver samples from patients with NASH also display a clear reduction in TUFM level, which correlates with increased MRG15 expression., Conclusion: Collectively, these findings uncover a mitochondrial MRG15-TUFM regulatory pathway that contributes significantly to progression from simple steatosis to NASH, and which could potentially be targeted to treat NASH., Lay Summary: The incidence of non-alcoholic fatty liver disease and its progressive form non-alcoholic steatohepatitis (NASH) is increasing, posing a significant global health challenge. Herein, we have uncovered the importance of the MRG15-TUFM pathway in NASH development. This pathway is active in the mitochondria (energy powerhouse of the cell) and could be targeted for the treatment of NASH., Competing Interests: Conflict of interest The authors declare no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) has been shown in many observational studies, but these conclusions remain controversial. Hence, we performed a meta-analysis to elucidate the association., Methods: A comprehensive search was conducted on relevant studies published from inception to December 31, 2018, in PubMed, EMBASE, and Web of Science databases. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled by random-effect model, generic inverse variance method. Subgroup and sensitivity analyses were also done. Publication bias was estimated by the funnel plot, Begg's test, and Egger's test., Results: Fifteen studies (eleven cross-sectional, two case-control, and two cohort studies) were included in this meta-analysis. The pooled OR of NAFLD in patients with H. pylori infection was 1.19 (95% CI: 1.11-1.29, P < 0.00001) when compared with the patients without H. pylori infection. Similar results were observed when the subgroup analyses were stratified by different geographical locations, study designs, and confounders adjustment. In subgroup analysis stratified by different H. pylori testing methods, the correlation still exists when using UBT, serology, RUT, or SAT, but there was no statistically significant difference when using multiple detection methods (OR = 2.96, 95% CI: 0.37-23.94, P = 0.31). Sensitivity analyses showed that our results were robust. No evidence of substantial publication bias was detected., Conclusions: Current evidence indicated that a positive association between H. pylori infection and the risk of NAFLD. Further prospective studies are warranted to strengthen the association and to clarify whether there is a causative link between them., (© 2019 John Wiley & Sons Ltd.)

Objective: To investigate the effect of Hugan Qingzhi tablets on lipid metabolism and inflammation in rats fed on high-fat diet and explore the underlying mechanisms., Methods: Sixty male Sprague-Dawley rats were randomly divided into 6 groups, namely HFD group (with high-fat diet and distilled water), control group (with normal diet and distilled water), fenofibrate group (with high-fat diet and treatment with 0.1 g

Background: Numerous recent studies have explored the association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of various extrahepatic cancers. However, the conclusions were inconclusive. The aim of this study was to clarify this relationship by conducting a robust meta‐analysis. Methods: Systematic searches were conducted on PubMed, Embase and Web of Science databases to identify relevant cohort studies published prior to February 2024. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were combined using a random‐effects model in this meta‐analysis. Results: Eighteen cohort studies (approximately 16.7 million participants) were finally included in this meta‐analysis. MASLD was linked to a higher risk of extrahepatic cancers, such as gastric (n = 10, HR = 1.47, 95% CI: 1.07–2.01), colorectal (n = 13, HR = 1.33, 95% CI: 1.16–1.53), pancreatic (n = 8, HR = 1.41, 95% CI: 1.11–1.79), biliary tract (n = 5, HR = 1.27, 95% CI: 1.18–1.37), thyroid (n = 6, HR = 1.46, 95% CI: 1.02–2.09), urinary system (n = 10, HR = 1.45, 95% CI: 1.25–1.69), breast (n = 11, HR = 1.17, 95% CI: 1.08–1.26) and female genital organ cancers (n = 10, HR = 1.36, 95% CI: 1.11–1.66). However, there was no statistically significant association between MASLD and the risk of head and neck (n = 6, HR = 1.03, 95% CI: 99–1.07), oesophageal (n = 9, HR = 1.26, 95% CI: 0.86–1.86), lung (n = 9, HR = 1.01, 95% CI: 0.92–1.10), prostate (n = 9, HR = 1.06, 95% CI: 0.94–1.19) or small intestine cancer (n = 2, HR = 1.75, 95% CI: 1.00–3.06). Conclusions: This latest large‐scale meta‐analysis indicated that MASLD was associated with an increased risk of various extrahepatic cancers, such as gastric, colorectal, pancreatic, biliary duct, thyroid, urinary system, breast, skin and female genital cancers. Further research is needed to investigate the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]