Metabolism, Journal Year: 2024, Volume and Issue: 161, P. 156043 - 156043
Published: Sept. 30, 2024
Language: Английский
Citations
9Pharmacotherapeutic options for metabolic dysfunction-associated steatotic liver disease: where are we today?
Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(9), P. 1249 - 1263
Published: June 12, 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in steatohepatitis (MASH) fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating drivers.
Language: Английский
Citations
8Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Oct. 14, 2024
GDF15 and FGF21, stress-responsive cytokines primarily secreted from the liver, are promising therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). However, interaction between FGF21 remains unclear. We examined effects of hepatocyte-specific or overexpression in high-fat diet (HFD)-fed mice 8 weeks. Hydrodynamic injection sustained high circulating levels respectively, resulting marked reductions body weight, epididymal fat mass, insulin resistance, hepatic steatosis. In addition, treatment led to early reduction weight despite no change food intake, indicating role other than appetite loss. increased liver-derived serum levels, whereas did not affect expression. promoted eIF2α phosphorylation XBP1 splicing, leading induction. murine AML12 hepatocytes treated with free fatty acids (FFAs), upregulated Fgf21 mRNA splicing. Overall, continuous exposure excess FFAs resulted a gradual increase β-oxidation-derived reactive oxygen species endoplasmic reticulum stress, suggesting that enhanced this pathway induced GDF15- FGF21-related crosstalk is an important MASLD.
Language: Английский
Citations
3
Liver International, Journal Year: 2025, Volume and Issue: 45(3)
Published: Feb. 3, 2025
ABSTRACT Background and Aims Liver‐related complications are frequent in patients with metabolic diseases, limited treatment options currently available. This systematic review meta‐analysis aimed to assess the effect of fibroblast growth factor‐21 (FGF21) analogues on hepatic steatosis, inflammation fibrosis diseases. Methods We conducted a literature search Pubmed, Scopus Web Science for randomised controlled trials (RCTs) assessing FGF21 steatosis evaluated by fat fraction (HFF), compared placebo. Adverse events (AEs) were also recorded. Results Treatment was associated metabolic‐associated steatohepatitis (MASH) resolution without worsening (5 studies, risk ratio [RR] 4.40, 95% confidence interval [CI]: 2.41, 8.03, p < 0.001) improvement 1 grade MASH (6 RR 1.79, CI: 1.24, 2.59, = 0.002). significantly lowered HFF placebo SMD ‐1.08, −1.28, −0.88, 0.001), while receiving more likely exhibit reduction 30% (10 4.08, 3.08, 5.40, or 50% 10.43, 5.47, 19.87, 0.001). normalisation (≤ 5%) frequently achieved 14.58, 4.70, 45.18, The results remained robust after sensitivity analyses. Serious AE leading drug discontinuation similar Conclusions can reduce representing possible option steatotic liver disease.
Language: Английский
Citations
0Dawn of an era of effective treatments for MAFLD
Portal hypertension & cirrhosis, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 24, 2024
Abstract Fatty liver disease is a commonly occurring resulting in hepatic and extrahepatic complications. To date, there have been few available treatments beyond conventional lifestyle modification. While modifications weight loss >10% shown to be beneficial for metabolic dysfunction‐associated steatohepatitis (MASH), the majority of patients, this difficult achieve. The recent approval resmetirom (a thyroid hormone receptor beta agonist) by Food Drug Administration following positive results histological outcomes phase 3 trial has opened door new (dysfunction)‐associated fatty (MAFLD) MASH. There are currently number trials targeting variety signaling pathways involved pathogenesis that also promising. This review focuses on MAFLD MASH, ongoing clinical trials, unresolved controversies area.
Language: Английский
Citations
1Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials
Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11
Published: April 5, 2024
The efficacy of Pegbelfermin (PGBF) in treating non-alcoholic steatohepatitis (NASH) remains controversial. Therefore, we conducted a dose-response meta-analysis to explore the effect and pattern PGBF at different dosages treatment durations on transaminase reduction NASH patients. We searches PubMed, Embase, Cochrane Library, Web Science, ClinicalTrials.gov, supplemented search with gray literature manual searches. Randomized controlled trials (RCTs) evaluating patients were included. Risk bias was assessed by Bias Tool 2.0. used random-effects models, generalized least squares regression, constrained maximum likelihood, restricted cubic splines relationship. Egger's linear regression employed assess publication bias. study is registered PROSPERO, CRD42023448024. Four RCT studies from period 2018-2023, involving 546 participants, No participants discontinued due adverse events. High-dose significantly reduced levels compared low-dose group (ALT %: MD = 14.94, 95% CI 2.11-27.77; AST 9.05, 3.17-14.92). Longer duration further decreased (ALT%: 8.81, 4.07-13.56; AST%: 6.72, 2.62-10.81). test did not reveal significant (p > 0.05). Further investigation indicated ceiling dosage 30 mg/week, experienced rebound after 28 weeks continuous treatment. There positive correlation between within certain range, showing an overall non-linear This finding provides guidance for clinical application PGBF. Clinicians should be mindful mg/week monitor changes timely adjustments dosage. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=448024.
Language: Английский
Citations
1Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: April 5, 2024
Abstract GDF15 and FGF21, stress-responsive cytokines primarily secreted from liver, are promising therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interaction between FGF21 remains unclear. We examined effect of hepatocyte-specific or overexpression in high-fat diet (HFD)-fed mice 8 weeks. Hydrodynamic injection sustained high circulating levels respectively, resulting marked reductions body weight, epididymal fat mass, insulin resistance, hepatic steatosis. Interestingly, treatment led to early reduction weight despite no change food intake, indicating role other than appetite loss. increased liver-derived serum levels, but did not affect expression. promoted eIF2α phosphorylation splicing XBP1s, leading induction. In murine AML12 hepatocytes treated with free fatty acids, also upregulated Fgf21 mRNA XBP1 splicing. Taken together, excess FFAs flooding resulted a gradual increase β-oxidation-derived reactive oxygen species ER stress, suggesting that enhanced this pathway induced expression FGF21. The GDF15- FGF21-related crosstalk is an important MASLD.
Language: Английский
Citations
0Liver Steatosis: From Lipotoxicity to Cellular Damage
Published: Jan. 1, 2024
Language: Английский
Citations
0