Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression.
Methods: Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018.
Results: The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss.
Conclusions: Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00535-019-01633-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of 11β-hydroxysteroid dehydrogenase type 1 inhibition in the antiobesity effect of J2H-1702 on adipocytes and a high-fat diet-induced NASH model.
Eur J Pharmacol
January 2025
College of Korean Medicine, Gachon University, Seongnam 13120, Korea. Electronic address:
Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.
View Article and Find Full Text PDFZearalenone exacerbates lipid metabolism disorders by promoting liver lipid droplet formation and disrupting gut microbiota.
Ecotoxicol Environ Saf
January 2025
Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety),Ministry of Agriculture and Rural Affairs of the P.R. China, Beijing 100083, China. Electronic address:
Zearalenone (ZEA), produced by Fusarium, is a fungal toxin commonly found in maize, wheat, and other cereals. ZEA has the ability to bind to estrogen receptors of humans and animals and is an environmental endocrine disruptor that may interfere with glucose homeostasis and lipid metabolism. In this study, we first investigated the effects of chronic exposure to low doses of ZEA with a high-fat-diet (HFD) in obese C57BL/6 J mice.
View Article and Find Full Text PDFAims: To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis.
Materials And Methods: In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks.
Bacillus subtilis HGCC-1 improves growth performance and liver health via regulating gut microbiota in golden pompano.
Anim Microbiome
January 2025
China-Norway Joint Lab on Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
Probiotics as green inputs have been reported to regulate metabolism and immunity of fish. However, the mechanisms by which probiotics improve growth and health of fish are unclear. Therefore, the aim of this study was to investigate the effect of Bacillus subtilis HGCC-1, an indigenous probiotic isolated from fish, on growth performance, host lipid metabolism, liver inflammation and gut microbiota of golden pompano.
View Article and Find Full Text PDFPopulation Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRAS Mutation from Phase 1 and Phase 2 Studies.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!