Highlights
- TGen researchers identified EV proteins — including INHBE, AFM, and complement C4A — correlated with hepatic steatosis in postmenopausal women.
- The study analyzed blood samples from 275 postmenopausal women enrolled in the Michigan site of the Study of Women's Health Across the Nation.
- Protein signatures differed between Black and non-Hispanic White women, which researchers say may point to a protective mechanism against liver disease.
- MASLD rates among U.S. women rose from 18.5% in 1988–1994 to 24.9% in 2007–2014, according to data cited in the paper.
Researchers at the Translational Genomics Research Institute (TGen), part of City of Hope, have identified distinct protein signatures in extracellular vesicles linked to liver fat accumulation in postmenopausal women, according to a study published in BMC Medicine on Tuesday, Dec. 16, 2025.
Extracellular vesicles, or EVs, are tiny, naturally occurring packages that help cells share proteins, metabolites, and other materials. The TGen team analyzed the protein contents of EVs drawn from circulating blood in 275 postmenopausal women — including 75 individuals with hepatic steatosis — enrolled in the Michigan site of the Study of Women's Health Across the Nation (MI-SWAN). Among 469 detected EV proteins, the researchers identified several correlated with hepatic steatosis, including complement C4A, AFM, and INHBE.
The study also found that EV protein cargo differed between non-Hispanic White women and Black women with hepatic steatosis. "African Americans, in general, have a lower susceptibility to steatotic liver disease, even in the presence of worse metabolic dysfunction," said Johanna K. DiStefano, Ph.D., a professor in TGen's Early Detection and Prevention Division, head of its Metabolic Disease Research Unit, and senior author of the paper. "The differences in proteins we observed between Black and White women may suggest a protective mechanism."
The INHBE protein was significantly elevated in EVs across all patient groups, including those with severe disease. Independent hepatic transcriptomic analysis further supported this finding, demonstrating a progressive increase in INHBE gene expression with worsening disease across the metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum, including metabolic dysfunction-associated steatohepatitis (MASH) and liver cirrhosis.
The research addresses a population that has received limited attention in liver disease studies. "With women specifically, we're seeing an increase in hepatic steatosis with menopause. Estrogen provides some protection against metabolic disease, including diabetes and heart disease, but when women lose that hormone in menopause, they lose that protection as well," DiStefano said. MASLD rates among U.S. women have risen from 18.5% in 1988–1994 to 24.9% in 2007–2014, according to data cited in the paper, and few routine, non-invasive tests exist for detecting the disease in its earlier stages.
"Our study suggests EV proteins such as INHBE and AFM may be good candidates for biomarkers of disease and contributors to MASLD in high-risk populations," said Patrick Pirrotte, Ph.D., associate professor at TGen, director of the Integrated Mass Spectrometry Shared Resource at TGen and City of Hope, and first author of the study. The researchers plan to further analyze the findings, according to the release.
Sources
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- tgen.org retrieved 2026-05-02T08:57:39.899345+00:00
Authored by Claude, drafted from primary-source material with beat-specific editorial guides at The Scottsdale Signal. Sources retrieved at 2026-05-02T08:57:39.899345+00:00. Every claim traces to a source. Reviewed before publish under our five-gate editorial process.
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