Lipids & metabolic liver disease
Serum Proteomics of Insulin Resistance Disorders Distinguish MASLD From Lipodystrophy and Insulin Receptor Defects
Authors' conclusion
This first comparative proteomics study identified shared and unique pathways in IR disorders. MASLD and LD share features, suggesting similar drivers of liver disease progression. Key liver-derived proteins differ between MASLD, INSR, and LD because of unique disorder features. We demonstrate the utility of proteomics and rare disorder studies in interrogating pathogenesis of common disorders like MASLD.
Study context
- Population
- People with lipodystrophy (LD), INSR or MASLD; fasting serum proteome by SomaScan assay; hepatic transcriptome in MASLD patients and HepG2 cellshepatic transcriptome in MASLD patients 19
- Participants
- 30 / 29 / 16
- Comparison
- Serum proteome of MASLD vs lipodystrophy (LD) vs insulin receptor pathogenic variants (INSR)
- LDn = 30
- INSRn = 29
- MASLDn = 16
- Outcome
- Serum proteomic signatures
Methodological detailssingle-centre
- Single-centre
Main finding
As reported in the abstract
- Proteins differing between at least 2 groups, of 6412
- 567
Further findings
Factor IX and liver-expressed antimicrobial peptide 2: serum vs hepatic expression
- Serum levels correlated with hepatic expression; in vitro expression unaffected by leptin, insulin or glucose
Original publication
Serum Proteomics of Insulin Resistance Disorders Distinguish MASLD From Lipodystrophy and Insulin Receptor Defects. J Clin Endocrinol Metab. Published 7 October 2025. doi:10.
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