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In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
Published on: July 19, 2024
Adipose Tissue Dysfunction in Metabolic Dysfunction-Associated Steatotic Liver Disease
Andrew John Legaspi Cruz1, Liyun Yuan1,2
1Department of Internal Medicine, Los Angeles County + USC Medical Center, Los Angeles, CA 90033, USA.
Cells
|August 13, 2026
Summary
Adipose tissue dysfunction contributes to variations in metabolic dysfunction-associated steatotic liver disease (MASLD) severity and progression. Understanding body composition phenotypes and adipose biology is crucial for targeted therapies in MASLD and metabolic dysfunction-associated steatohepatitis (MASH).
Area of Science:
- Hepatology and metabolic research
- Adipose tissue biology and dysfunction
- Clinical heterogeneity of liver disease
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) presents significant clinical heterogeneity, with patient outcomes varying despite similar demographic or fibrosis markers.
- Adipose tissue dysfunction is increasingly recognized as a key driver of this heterogeneity, influencing liver injury and fibrosis.
- Distinct body-composition phenotypes, including lean MASLD and sarcopenic visceral obesity, are associated with varying degrees of adipose dysfunction and disease risk.
Purpose of the Study:
- To review the role of adipose tissue dysfunction in MASLD.
- To explore the clinical relevance of different body-composition phenotypes in MASLD.
- To discuss recent therapeutic advancements in MASLD and metabolic dysfunction-associated steatohepatitis (MASH) through the lens of adipose-liver-muscle interactions.
Main Methods:
- Literature review of studies on adipose tissue dysfunction in MASLD.
- Analysis of body-composition phenotypes (lean MASLD, sarcopenic visceral obesity, myosteatosis, hypertriglyceridemic waist).
- Synthesis of recent therapeutic data for MASLD and MASH, considering mechanisms of action.
Main Results:
- Adipose dysfunction, assessed through depot quantification, fibrogenesis, insulin resistance, and adipokines, correlates with liver injury and fibrosis severity.
- Clinically recognizable body-composition phenotypes offer different insights into disease mechanisms and prognosis.
- Emerging therapies for MASH (e.g., resmetirom, semaglutide, tirzepatide, FGF21 analogs) highlight the importance of targeting adipose-mediated and liver-directed pathways.
Conclusions:
- Adipose tissue dysfunction is a critical determinant of MASLD heterogeneity and progression.
- Characterizing body-composition phenotypes can refine risk stratification and guide therapeutic strategies.
- Future treatments for MASLD and MASH should consider integrated approaches targeting adipose tissue, liver, and muscle biology.
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