White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy‐based therapy DOI
Peng Ye, Qihai Wang,

Wen‐Ye Kong

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(16), P. 2774 - 2793

Published: April 21, 2024

Abstract Background and Purpose White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. Experimental Approach WAT status of healthy adjuvant‐induced (AIA) rats were compared. The contribution to RA pathology was evaluated by pre‐adipocyte transplant experiments dissecting perirenal fat pads AIA rats. impact on investigated culturing pre‐adipocytes. Proteins differentially expressed identified the UPLC/MS 2 method. These together with PPARγ siRNA agonist used treat pre‐adipocytes vitro. medium for THP‐1 monocyte culture. Key Results Compared controls, smaller but secreted more leptin, eNAMPT, MCP‐1, TNF‐α, IL‐6. rat increased levels these adipokines recipients. patients' serum induced a similar secretion change impaired differentiation Adipectomy eased AIA‐related immune abnormalities arthritic manifestations. Hepatokines PON1, IGFBP4, GPIHBP1 among differential proteins high blood, inflammatory secretions inhibited expression caused impairment pre‐adipocytes, outcome PPARγ‐silencing. endowed cells ability activate monocytes, which can be abrogated rosiglitazone. Conclusion Implications Certain hepatokines potentiate expedite progression inhibiting PPARγ. Targeting this signalling or abnormal various approaches may reduce severity.

Language: Английский

Inter-organ crosstalk during development and progression of type 2 diabetes mellitus DOI Open Access
Georgia Xourafa,

Melis Korbmacher,

Michael Roden

et al.

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 27 - 49

Published: Oct. 16, 2023

Language: Английский

Citations

92

Endocrine aspects of metabolic dysfunction-associated steatotic liver disease (MASLD): Beyond insulin resistance DOI Creative Commons
Alan L. Hutchison, Federica Tavaglione, Stefano Romeo

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(6), P. 1524 - 1541

Published: Sept. 18, 2023

While the links between metabolic dysfunction associated steatotic liver disease (MASLD) and obesity, insulin resistance are widely appreciated, there a host of complex interactions other endocrine axes. it can be difficult to definitively distinguish direct causal relationships those attributable increased adipocyte mass, is substantial evidence indirect specific dysregulation severity MASLD. Strong effects exists for low levels growth hormone, sex hormones, thyroid hormone with development disease. The impact steroid e.g. cortisol dehydropepiandrosterone, adipokines much more divergent. Thoughtful assessment, based on individual risk factors findings, also management non-insulin axes should performed in evaluation Multiple therapeutic pharmaceutical targets have emerged that leverage various reduce fibroinflammatory cascade steatohepatitis (MASH).

Language: Английский

Citations

84

Epidemiology of Metabolic Dysfunction Associated Steatotic Liver Disease DOI Creative Commons
Zobair M. Younossi,

Markos Kalligeros,

Linda Henry

et al.

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

Published: Aug. 19, 2024

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does prevalence metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% all adults 7-14% children adolescents have MASLD. By 2040, MASLD rate for is projected over 55%. Although many with will not develop progressive disease, given vast number patients MASLD, it has now become top indication transplant in United States those hepatocellular carcinoma (HCC) women. However, most common cause mortality among remains death cardiovascular diseases. In addition outcomes (cirrhosis HCC), increased risk developing de-novo T2D, chronic kidney sarcopenia extrahepatic cancers. Furthermore, decreased health related quality life, work productivity, fatigue healthcare resource utilization substantial economic burden. Similar other lifestyle interventions heathy diet physical activity remain cornerstone managing these patients. a T2D drugs are available treat co-morbid Resmetirom only MASH-targeted medication that was recently approved by Federal Drug Administration use stage 2-3 fibrosis. The following review provides an overview epidemiology, its factors demonstrates without further global initiatives, may increase.

Language: Английский

Citations

44

Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications DOI
Matthias B. Schulze, Norbert Stefan

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: 20(11), P. 633 - 646

Published: June 27, 2024

Language: Английский

Citations

30

Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases DOI Creative Commons

Reddemma Sandireddy,

Suganya Sakthivel,

Priyanka Gupta

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 16, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty (NAFLD), is the most common disorder worldwide, with an estimated global prevalence of more than 31%. steatohepatitis (MASH), formerly (NASH), a progressive form MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide comprehensive analysis extrahepatic manifestations MASH, focusing on chronic diseases related cardiovascular, muscular, renal systems. A systematic published studies literature was conducted summarize findings systemic impacts MASH. The focused association MASH metabolic comorbidities, cardiovascular mortality, sarcopenia, kidney disease. Mechanistic insights into concept lipotoxic inflammatory "spill over" from MASH-affected were also explored. are highly associated (50%-80%) other comorbidities such impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, hypertension. Furthermore, 90% obese patients diabetes have Data suggest that in middle-aged individuals (especially those aged 45-54), independent risk factor for plays crucial role mediating pathological effects observed. Understanding multifaceted impact heart, muscle, early detection stratification. knowledge timely implementing management strategies addressing multi-organ involvement pathogenesis.

Language: Английский

Citations

24

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis DOI Creative Commons
Michael Cooreman, Javed Butler, Robert P. Giugliano

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 10, 2024

Abstract Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging histological grading) all original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting (FG), hs-CRP, ferritin, diastolic BP improved significantly, independent diabetes status: most prediabetes returned to normal FG levels. Significant adiponectin increases correlated CMH marker improvement; had an average weight gain 2.5 kg, 49% gaining ≥2.5% weight. Therapeutic benefits similar regardless change. Here, we show that effects MASH are accompanied improvement, indicative potential clinical benefits.

Language: Английский

Citations

21

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

Adipokines: masterminds of metabolic inflammation DOI
Herbert Tilg, Gianluca Ianiro, Antonio Gasbarrini

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Language: Английский

Citations

18

Adipokines regulate the development and progression of MASLD through organellar oxidative stress DOI Creative Commons
Ke Zhao, Heng Zhang,

Wenyu Ding

et al.

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 29, 2025

The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause chronic pathology globally, increasing. pathophysiological underpinnings its progression, currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes array adipokines that are modulated by dietary patterns and lifestyle choices. These intricately orchestrate regulatory pathways impact glucose lipid metabolism, stress, mitochondrial function, thereby influencing the evolution hepatic steatosis progression to steatohepatitis (MASH). This review examines recent data, underscoring critical interplay reactive oxygen species, redox signaling in adipokine-mediated mechanisms. role various regulating onset MASLD/MASH through dysfunction endoplasmic reticulum stress underlying mechanisms discussed. Due emerging correlation between development MASLD positions, these potential targets for innovative therapeutic interventions management. A comprehensive understanding pathogenesis instrumental identifying therapies MASH.

Language: Английский

Citations

3

The growing range of complications of diabetes mellitus DOI
Peter Shane Hamblin, Anthony Russell, Stella Talic

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2