Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The incidence of NAFLD has increased steadily due to its close association with the global epidemic of obesity and type 2 diabetes. However, there is no effective pharmacological therapy approved for NAFLD. Farnesoid X receptor (FXR), a member of the nuclear receptor subfamily, plays important roles in maintaining the homeostasis of bile acids, glucose, and lipids. FXR agonists have shown promise for the treatment of NAFLD. In this study, we report altenusin (2076A), a natural nonsteroidal fungal metabolite, as a novel selective agonist of FXR with an EC value of 3.2 ± 0.2 μM. Administration of 2076A protected mice from high-fat diet (HFD)-induced obesity by reducing the body weight and fat mass by 22.9% and 50.0%, respectively. Administration of 2076A also decreased the blood glucose level from 178.3 ± 12.4 mg/dl to 116.2 ± 4.1 mg/dl and the serum insulin level from 1.4 ± 0.6 ng/dl to 0.4 ± 0.1 ng/dl. Moreover, 2076A treatment nearly reversed HFD-induced hepatic lipid droplet accumulation and macrovesicular steatosis. These metabolic effects were abolished in FXR knockout mice. Mechanistically, the metabolic benefits of 2076A might have been accounted for by the increased insulin sensitivity and suppression of genes that are involved in hepatic gluconeogenesis and lipogenesis. In summary, we have uncovered a new class of nonsteroidal FXR agonist that shows promise in treating NAFLD and the associated metabolic syndrome.
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http://dx.doi.org/10.1124/mol.117.108829 | DOI Listing |
Cancer Rep (Hoboken)
January 2025
Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Background: Bioinformatics analysis of hepatocellular carcinoma (HCC) expression profiles can aid in understanding its molecular mechanisms and identifying new targets for diagnosis and treatment.
Aim: In this study, we analyzed expression profile datasets and miRNA expression profiles related to HCC from the GEO using R software to detect differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs).
Methods And Results: Common DEGs were identified, and a PPI network was constructed using the STRING database and Cytoscape software to identify hub genes.
Gut Microbes
December 2025
Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA.
There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system.
View Article and Find Full Text PDFScand J Gastroenterol
January 2025
Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Objectives: Indications of mitochondrial dysfunction are commonly seen in liver diseases, but data are scarce in primary sclerosing cholangitis (PSC). Analyzing circulating and liver-resident molecules indirectly reflecting mitochondrial dysfunction, we aimed to comprehensively characterize this deficit in PSC, and whether this was PSC specific or associated with cholestasis.
Materials And Methods: We retrospectively included plasma from 191 non-transplant patients with large-duct PSC and 100 healthy controls and explanted liver tissue extracts from 24 PSC patients and 18 non-cholestatic liver disease controls.
EClinicalMedicine
December 2024
Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK.
Background: Despite the availability of various pharmacological and behavioural interventions, alcohol-related mortality is rising. This systematic review aimed to critically evaluate the existing literature on the association between glucagon-like peptide-1 receptor agonists use (GLP-1 RAs) and alcohol consumption.
Methods: Electronic searches were conducted on Ovid Medline, EMBASE, PsycINFO, clintrials.
EClinicalMedicine
December 2024
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Background: Therapeutic advancements for the polyglutamine diseases, particularly spinocerebellar degeneration, are eagerly awaited. We evaluated the safety, tolerability, and therapeutic effects of L-arginine, which inhibits the conformational change and aggregation of polyglutamine proteins, in patients with spinocerebellar ataxia type 6 (SCA6).
Methods: A multicenter, randomized, double-blind, placebo-controlled phase 2 trial (clinical trial ID: AJA030-002, registration number: jRCT2031200135) was performed on 40 genetically confirmed SCA6 patients enrolled between September 1, 2020, and September 30, 2021.
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