Nutrients, Год журнала: 2024, Номер 16(20), С. 3571 - 3571
Опубликована: Окт. 21, 2024
: The diverse effects of fructose and glucose on the progression metabolic dysfunction-associated steatotic liver disease remain uncertain. This study investigated effects, in animal models, high-fat diets (HFDs) supplemented with either or fructose.
Язык: Английский
Metabolism, Год журнала: 2024, Номер 157, С. 155937 - 155937
Опубликована: Май 21, 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) closely associates with obesity and type 2 diabetes. Lifestyle intervention bariatric surgery aiming at substantial weight loss are cornerstones of MASLD treatment by improving histological outcomes reducing risks comorbidities. Originally developed as antihyperglycemic drugs, incretin (co-)agonists SGLT2 inhibitors also reduce steatosis cardiorenovascular events. Certain agonists effectively improve features MASLD, but not fibrosis. Of note, beneficial effects on may necessarily require loss. Despite moderate gain, one PPARγ agonist improved adipose tissue certain benefit fibrosis in post-hoc analyses. Likewise, the first THRβ-agonist was recently provisionally approved because significant improvements We here discuss liver-related metabolic induced different treatments their association Therefore, we compare results from clinical trials drugs acting via (incretin (co)agonists, inhibitors) those exerting no (pioglitazone; resmetirom). Furthermore, other development directly targeting hepatic lipid metabolism (lipogenesis inhibitors, FGF21 analogs) addressed. Although THRβ-agonism outcomes, concepts should consider all cardiometabolic risk factors for effective reduction morbidity mortality affected people.
Язык: Английский
Процитировано
33
Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер 60(11-12), С. 1525 - 1533
Опубликована: Окт. 16, 2024
ABSTRACT Background Semaglutide, a glucagon‐like peptide‐1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction‐associated steatohepatitis (MASH). Aims To describe the trial design and baseline characteristics of ‘Effect Semaglutide Subjects with Non‐cirrhotic Non‐alcoholic Steatohepatitis’ (ESSENCE) (NCT04822181). Methods ESSENCE is two‐part, phase 3, randomised, multicentre evaluating effect subcutaneous semaglutide 2.4 mg participants biopsy‐proven MASH fibrosis stage 2 or 3. The primary objective Part 1 to demonstrate that improves liver histology compared placebo. two endpoints are: resolution no worsening fibrosis, improvement steatohepatitis. based on clinical outcomes. current work reports first 800 randomised which includes demographics, laboratory parameters, histology, non‐invasive tests presence steatotic disease (MASLD) cardiometabolic criteria. Results Of participants, 250 (31.3%) had 550 (68.8%) In overall population, mean (standard deviation [SD]) age was 56 (11.6) years, 57.1% were female, (SD) body mass index 34.6 (7.2) kg/m , 55.5% type diabetes > 99% at least one MASLD criterion according published definition. Conclusion population clinically significant stages Although criteria not requirement for study enrolment, almost all (> 99%) criterion. Trial Registration NCT04822181
Язык: Английский
Процитировано
24
Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Авг. 26, 2024
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health problem owing to its high prevalence and associated morbidity mortality secondary progressive cardiovascular events. Resmetirom, a selective thyroid hormone receptor-β agonist has been developed as therapeutic modality for MASLD. This systematic review meta-analysis aimed evaluate the effectiveness safety of resmetirom compared placebo in treatment Eligible studies were systematically identified by screening PubMed, Scopus, Web Science, Cochrane library, Embase, ClinicalTrials.gov from 2014 2024. Only randomized controlled trials comparing efficacy MASLD against included analysis. Meta-analysis was performed using RevMan 5.4 software. Four with low risk bias involving total 2359 participants identified. The metanalysis only three clinical 2234 participants. A significant reduction MRI-proton density fat fraction (MRI-PDFF) 80 mg Resmetirom that [SMD − 27.74 (95% CI 32.05 32.42), p < 0.00001] at 36–52 weeks well 12–16 30.92 36.44 25.40), 0.00001]. With 100 dose 36.05 40.67 31.43), 36.89 40.73 33.05), observed. LDL-c triglyceride, lipoproteins. enzymes. There FT4 increase SHBG sex steroids placebo. no major difference overall emergent adverse events [OR 1.55 0.84 2.87), 1.13 0.78 1.63), doses However, gastrointestinal diarrhoea nausea occurred ≥ 10% group 12 week. showed modest treating MRI-PDFF, LDL-c, lipoproteins, enzymes NASH biomarkers without concerns. Larger long-term RCTs may further confirm this promising outcomes use
Язык: Английский
Процитировано
10
Clinical Nutrition, Год журнала: 2024, Номер 43(12), С. 391 - 404
Опубликована: Ноя. 14, 2024
Язык: Английский
Процитировано
4
Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 334023
Опубликована: Ноя. 26, 2024
Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed the treatment of type 2 diabetes mellitus obesity, they were one first drug classes to be examined individuals with MASLD/MASH. Successful phase randomised clinical trials these agents resulted progression 3 (principally testing long-term efficacy subcutaneous semaglutide). Over last few years, addition GLP-1RAs, newer glucose-dependent insulinotropic peptide and/or glucagon agonist functions tested, increasing evidence from histological improvements MASLD/MASH, as well benefits on MASLD-related extrahepatic complications. Based this background evidence, single, dual or triple incretin are becoming an attractive promising option MASLD MASH, particularly coexisting obesity mellitus. In narrative review, we examine rapidly expanding body supporting role incretin-based pharmacotherapies delaying reversing MASH progression. We also discuss biology incretins putative hepatoprotective mechanisms managing MASH.
Язык: Английский
Процитировано
4
Toxicology Reports, Год журнала: 2025, Номер 14, С. 101895 - 101895
Опубликована: Янв. 18, 2025
Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, satiety. We examine compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) managing type 2 diabetes (T2D), obesity, other The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated (MAPK), C (PKC). Expanding our understanding, investigates potential role cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators gene expression, introduced modulators signaling. delve link between miRNAs T2D obesity explore specific miRNA examples influencing GLP-1R function. Finally, explores rationale seeking alternatives to highlights natural products modulatory effects.
Язык: Английский
Процитировано
0
Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер 752, С. 151466 - 151466
Опубликована: Фев. 8, 2025
Язык: Английский
Процитировано
0
Biomolecules, Год журнала: 2025, Номер 15(4), С. 469 - 469
Опубликована: Март 22, 2025
With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence proposed microbiota-derived metabolites short-chain fatty acids (SCFAs) potential factor in pathophysiology of MASLD and related conditions, such obesity type 2 diabetes mellitus (T2DM). By influencing key pathways involved energy homeostasis, insulin sensitivity, inflammation, SCFAs play an important role gut microbiota composition, intestinal barrier function, immune modulation, direct signaling. Furthermore, recent animal human studies on therapeutic strategies targeting demonstrate their for treating these disorders.
Язык: Английский
Процитировано
0
Trends in Endocrinology and Metabolism, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
World Journal of Gastroenterology, Год журнала: 2024, Номер 30(43), С. 4682 - 4688
Опубликована: Окт. 31, 2024
The gut-liver axis plays a crucial role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Key metabolites, including lipopolysaccharides, short-chain fatty acids (SCFAs), bile acids, beneficial gut bacteria such as Bifidobacterium Lactobacillus, are pivotal this process. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise managing MASLD by promoting weight loss, enhancing insulin secretion, improving health. They restore functionality, their effects amplified through dietary modifications microbiome-targeted therapies. Emerging research highlights interplay between GLP-1 RAs microbiota, indicating that microbiome significantly influences therapeutic outcomes. Metabolites produced bacteria, can stimulate glucagon-like (GLP-1) further Integrating interventions with RA treatment may enhance health modulating microbiota-SCFAs-GLP-1 pathway. Future is needed to understand personalized effects, prebiotics probiotics offering avenues for MASLD.
Язык: Английский
Процитировано
1