PNPLA3 gene variation modulates diet-induced improvement in liver lipid content in type 2 diabetes DOI Creative Commons
Kalliopi Pafili, Oana‐Patricia Zaharia, Klaus Straßburger

et al.

Clinical Nutrition, Journal Year: 2025, Volume and Issue: 48, P. 6 - 15

Published: March 6, 2025

Language: Английский

NAFLD and NASH: etiology, targets and emerging therapies DOI

Shulin Wei,

Li Wang, Paul C. Evans

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(3), P. 103910 - 103910

Published: Feb. 1, 2024

Language: Английский

Citations

66

Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment DOI Creative Commons
Norbert Stefan, Hannele Yki‐Järvinen, Brent A. Neuschwander‐Tetri

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

29

Metabolic dysfunction-associated steatotic liver disease in adults DOI
Daniel Q. Huang, Vincent Wai‐Sun Wong, Mary E. Rinella

et al.

Nature Reviews Disease Primers, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 6, 2025

Language: Английский

Citations

12

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials DOI

Javier Armisen,

Mitra Rauschecker,

Janeli Sarv

et al.

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

8

Integrative Metabolism in MASLD and MASH: Pathophysiology and Emerging Mechanisms DOI Creative Commons
Gregory R. Steinberg, Celina M Valvano, William De Nardo

et al.

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The liver acts as a central metabolic hub, integrating signals from the gastrointestinal tract and adipose tissue to regulate carbohydrate, lipid, amino acid metabolism. Gut-derived metabolites, such acetate ethanol non-esterified fatty acids white (WAT), influence hepatic processes, which rely on mitochondrial function maintain systemic energy balance. Metabolic dysregulation obesity, insulin resistance, type 2 diabetes disrupt these pathways, leading dysfunction-associated steatotic disease (MASLD) steatohepatitis (MASH). This review explores fluxes within gut-adipose tissue-liver axis, focusing pivotal role of de novo lipogenesis (DNL), dietary substrates like glucose fructose, changes in during MASLD progression. It highlights contributions resistance impaired dynamics lipid accumulation. Further understanding how interplay between substrate flux gastro-intestinal integrates with intersects structural functional alterations mitochondria will be important identify novel therapeutic targets advance treatment MASH.

Language: Английский

Citations

4

Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics DOI Creative Commons
Yuxiao Jiang, Lili Wu,

Xiaopeng Zhu

et al.

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 2, 2024

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic that affects over 30% world’s population. For decades, heterogeneity non-alcoholic fatty (NAFLD) has impeded our understanding mechanism and development effective medications. However, a recent change in nomenclature from NAFLD to MASLD emphasizes critical role systemic metabolic dysfunction pathophysiology this therefore promotes progress pharmaceutical treatment MASLD. In review, we focus on underlying abnormality hepatic lipid metabolism patients with MASLD, summarize latest therapeutic medications target disorders.

Language: Английский

Citations

14

Diabetes as a risk factor for MASH progression DOI Creative Commons

Sofiya Gancheva,

Michael Roden, Laurent Castéra

et al.

Diabetes Research and Clinical Practice, Journal Year: 2024, Volume and Issue: 217, P. 111846 - 111846

Published: Sept. 6, 2024

Language: Английский

Citations

13

From MASH to HCC: the role of Gas6/TAM receptors DOI Creative Commons
Daria Apostolo, Luciana Louzada Ferreira,

Federica Vincenzi

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 17, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic (NASH). It characterized by inflammation and injury of liver in presence cardiometabolic risk factors may eventually result development hepatocellular carcinoma (HCC), most common form primary cancer. Several pathogenic mechanisms are involved transition from MASH HCC, encompassing metabolic injury, inflammation, immune dysregulation fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) TAM (Tyro3, Axl, MerTK) receptors play important roles. The Gas6/TAM family modulation lipid metabolism, fibrosis, tumor progression metastasis, processes which an role pathophysiology acute chronic diseases. review, we discuss MASH-associated HCC potential involvement system disease progression. addition, since therapeutic strategies limited, also speculate regarding possible future treatments involving targeting or receptors.

Language: Английский

Citations

10

Hepatic mitochondrial reductive stress in the pathogenesis and treatment of steatotic liver disease DOI Creative Commons

Mari J. Jokinen,

Panu K. Luukkonen

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(4), P. 319 - 334

Published: March 12, 2024

Steatotic liver diseases (SLDs) affect one-third of the population, but pathogenesis underlying these is not well understood, limiting available treatments. A common factor in SLDs increased hepatic mitochondrial reductive stress, which occurs as a result excessive lipid and alcohol metabolism. Recent research has also shown that genetic risk factors contribute to this stress. This review aims explore how increase stress it disrupts metabolism, leading SLDs. Additionally, will discuss latest clinical studies on pharmaceutical treatments for SLDs, specifically peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, thyroid hormone (THR) acetyl-CoA carboxylase (ACC) inhibitors, uncouplers. These have effect decreasing been largely overlooked.

Language: Английский

Citations

10

Precision medicine and nucleotide-based therapeutics to treat MASH DOI Creative Commons
Andrea Caddeo, Stefano Romeo

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex multifactorial and becoming the leading cause of liver-related morbidity mortality. MASLD spans from isolated steatosis to metabolic steatohepatitis (MASH), that may progress cirrhosis hepatocellular carcinoma (HCC). Genetic, metabolic, environmental factors strongly contribute heterogeneity MASLD. Lifestyle intervention weight loss represent viable treatment for Moreover, Resmetirom, thyroid hormone beta receptor agonist, has recently been approved treatment. However, most individuals treated did not respond this therapeutic suggesting need more tailored approach treat Oligonucleotide-based therapies, namely small-interfering RNA (siRNA) antisense oligonucleotide (ASO), have developed tackle by reducing expression genes influencing MASH progression, such as PNPLA3 HSD17B13. Here, we review latest made in synthesis development oligonucleotide-based agents targeting genetic determinants MASH.

Language: Английский

Citations

10