GLP-1 Receptor Agonist Improves Metabolic Disease in a Pre-clinical Model of Lipodystrophy DOI Creative Commons
Ahlima Roumane, George D. Mcilroy, Nadine Sommer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 5, 2023

ABSTRACT Individuals with lipodystrophies typically suffer from significant metabolic disease linked to adipose tissue dysfunction including severe insulin resistance and lipoatrophic diabetes, hepatic steatosis hyperphagia. Current treatment options are limited beter therapies for affected individuals urgently needed. No systematic, detailed analyses exist of the effects glucagon like peptide-1 receptor (GLP-1R) agonists in diabetes. Here we examined GLP-1R agonist liraglutide seipin knockout mice, a pre-clinical model generalised lipodystrophy. Acute mice significantly improved insulin, glucose pyruvate tolerance. Once-daily injection 14 days led modest reduction food intake but improvements hepatomegaly associated reduced markers liver fibrosis. Detailed examination pancreas revealed that enhanced secretion response challenge concomitantly control. Thus, multiple aspects diabetes congenital This provides important insights regarding benefits treating lipodystrophy, informing more widespread use improve health this condition.

Language: Английский

From non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD): an ongoing journey towards refining the terminology for this prevalent metabolic condition and unmet clinical need DOI
Michail Kokkorakis, Chrysoula Boutari, Niki Katsiki

et al.

Metabolism, Journal Year: 2023, Volume and Issue: 147, P. 155664 - 155664

Published: July 28, 2023

Language: Английский

Citations

42
Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies DOI Open Access
Michail Kokkorakis, Emir Muzurović, Špela Volčanšek

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

Citations

30
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

19
Circulating hormones in biopsy-proven steatotic liver disease and steatohepatitis: A Multicenter Observational Study DOI
Laura Valenzuela‐Vallejo, Pavlina Chrysafi, Matina Kouvari

et al.

Metabolism, Journal Year: 2023, Volume and Issue: 148, P. 155694 - 155694

Published: Sept. 25, 2023

Language: Английский

Citations

18
Thyroid function, adipokines and mitokines in metabolic dysfunction‐associated steatohepatitis: A multi‐centre biopsy‐based observational study DOI Creative Commons
Matina Kouvari, Laura Valenzuela‐Vallejo,

Evangelos Axarloglou

et al.

Liver International, Journal Year: 2024, Volume and Issue: 44(3), P. 848 - 864

Published: Jan. 23, 2024

Abstract Background and Aims Thyroid axis is currently under investigation as a therapeutic target in metabolic dysfunction‐associated steatotic liver disease (MASLD). function was examined herein the full spectrum of disease. Methods Subjects were recruited had biopsies two Gastroenterology‐Hepatology Clinics (Greece Australia) one Bariatric‐Metabolic Surgery Clinic (Italy). The main working sample n = 677 subjects with MASLD after excluding abnormal free thyroxine levels. Participants classified according to thyroid‐stimulating hormone (TSH) standard criteria: Subclinical hyperthyroidism (<0.4 uIU/mL); Euthyroidism relatively low (0.4 <2.5 euthyroidism high (2.5–4.0 subclinical hypothyroidism (>4 uIU/mL). Results TSH continuous variable positively associated significant fibrosis ( F ≥ 2), steatohepatitis (MASH) at‐risk MASH. 2 (odds ratio [OR] 3.47, 95% confident interval [CI] [1.50, 8.05], p .02), MASH (OR 3.44, CI [1.48, 7.98] .001) 3.88, [1.76, 8.55], .001), before controlling for adiposity, central obesity, insulin resistance. When leptin, adiponectin, or growth differentiation factor‐15 moderators, significance lost. Sex‐specific analysis revealed strong association between presence among women, eliminated only when adipokines/mitokines adjusted for. Restricted cubic spline associations outcomes ‐values < .01) inflection points being 2.49, 2.67 6.96. Conclusions These observations provide support studies on administration thyroid therapeutics liver‐specific receptor agonists across continuum.

Language: Английский

Citations

7
GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy DOI Creative Commons
Ahlima Roumane, George D. Mcilroy, Nadine Sommer

et al.

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

Published: April 30, 2024

Aims Individuals with lipodystrophies typically suffer from metabolic disease linked to adipose tissue dysfunction including lipoatrophic diabetes. In the most severe forms of lipodystrophy, congenital generalised may be almost entirely absent. Better therapies for affected individuals are urgently needed. Here we performed first detailed investigation effects a glucagon like peptide-1 receptor (GLP-1R) agonist in diabetes, using mice lipodystrophy. Methods Lipodystrophic insulin resistant and glucose intolerant seipin knockout were treated GLP-1R liraglutide either acutely preceding analyses tolerance or chronically prior phenotyping ex vivo studies. Results Acute treatment significantly improved insulin, pyruvate tolerance. Once daily injection 14 days led significant improvements hepatomegaly associated steatosis reduced markers liver fibrosis. Moreover, enhanced secretion response challenge concomitantly control. Conclusions diabetes hepatic This provides important insights regarding benefits agonists treating informing more widespread use improve health this condition.

Language: Английский

Citations

6
Urbanization as a Driving Factor of Global Burden of Non-Alcoholic Fatty Liver Disease: Based on the Global Burden of Disease Study 2021 DOI

Zejin Ou,

Shi Chen, Ziyi Wang

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Causal relationship analysis of MRI measurements of major human internal organs and liver disease DOI Creative Commons
Huanyu Wu, Daoguo Zhou, Jiayuan Zhu

et al.

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 11, 2025

This study aimed to explore the causal association between imaging measurement indicators of major internal organs and liver lesions using a two-sample Mendelian randomization (MR) method. Data from UK Biobank GWAS Catalog platform were used select single nucleotide polymorphisms (SNPs) associated with MRI or derived results various organ as genetic instrumental variables. FinnGen project's R9 version lesion outcomes, such nonalcoholic fatty disease (NAFLD), cirrhosis, primary hepatocellular carcinoma (HCC). UVMR analysis utilized variable-by-variable, MVMR was adjust for confounding on significant Steiger directional test, heterogeneity, pleiotropy, sensitivity tests conducted enhance reliability. Univariate (UVMR) indicated that volume (LV), fat (LF), subcutaneous adipose tissue (SATM) are risk factors NAFLD. The multivariable MR (MVMR) NAFLD showed LV LF remained significant, while SATM did not. For cirrhosis (NAC), suggested LV, LF, factors, but only significant. Additionally, pancreatic (PV) found be protective factor, splenic (SV) pathogenic factor NAC. HCC, both analyses iron (LI) not remain in analysis. In NAC stage, additional effects PV SV observed. related LI support effect HCC stage.

Language: Английский

Citations

0
The current status and future directions of artificial intelligence in the prediction, diagnosis, and treatment of liver diseases DOI Creative Commons
Bo Gao, Wendu Duan

Digital Health, Journal Year: 2025, Volume and Issue: 11

Published: April 1, 2025

Early detection, accurate diagnosis, and effective treatment of liver diseases are paramount importance for improving patient survival rates. However, traditional methods frequently influenced by subjective factors technical limitations. With the rapid progress artificial intelligence (AI) technology, its applications in medical field, particularly prediction, diseases, have drawn increasing attention. This article offers a comprehensive review current AI hepatology. It elaborates on how is utilized to predict progression diagnose various conditions, assist formulating personalized plans. The emphasizes key advancements, including application machine learning deep algorithms. Simultaneously, it addresses challenges limitations within this domain. Moreover, pinpoints future research directions. underscores necessity large-scale datasets, robust algorithms, ethical considerations clinical practice, which crucial facilitating integration technology enhancing diagnostic therapeutic capabilities diseases.

Language: Английский

Citations

0
Tailored Model of Care for Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease DOI
Mohamed El‐Kassas,

Abeer Awad,

Mohamed Elbadry

et al.

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: 44(01), P. 054 - 068

Published: Jan. 25, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty (NAFLD), is increasing globally, creating a growing public health concern. However, this often not diagnosed, and accurate data on its epidemiology are limited in many geographical regions, making it challenging to provide proper care implement effective national plans. To combat the burden, screening diagnosis must reach significant number of high-risk subjects. Addressing MASLD challenge requires multidisciplinary approach involving prevention, diagnosis, treatment, care, with collaboration between multiple stakeholders system. This be guided by global strategies, combined efficient models developed through bottom-up process. review article highlights pillars model (MoC), including screening, risk stratification, establishing clinical pathway for management, addition discussing impact nomenclature change proposed MoC.

Language: Английский

Citations

3