Analysis of extracellular vesicle cargo finds differences between Black and White women
Extracellular vesicles (EVs), tiny, naturally occurring packages that help cells share proteins, metabolites, and other materials, have distinct protein signatures related to liver fat in postmenopausal women, according to a new study led by researchers from Translational Genomics Research Institute (TGen), part of City of Hope.
The analysis published in BMC Medicine also found EV protein signatures differed in women based on race (Black vs White) and disease severity.
Together, the findings offer a unique glimpse at how metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) may develop in postmenopausal women, an understudied group in liver disease.
“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,” 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.
Recent studies show that MASLD rates have risen sharply among U.S. women, increasing from 18.5% in 1988-1994 to 24.9% in 2007-2014. However, there are few routine, non-invasive tests for detecting the disease, especially in its earlier stages.
Following other research suggesting that EVs might reflect or even drive steatosis progression, DiStefano and colleagues 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 proteins that were correlated with hepatic steatosis, including complement C4A, AFM and INHBE. Further analysis found that the protein cargo in EVs differed between non-Hispanic White women and Black women with hepatic steatosis.
These findings suggest that EVs could be capturing multiple influences relevant to MASLD, potentially including ancestry-related genetics and environmental factors, the research team noted in their paper.
“African Americans, in general, have a lower susceptibility to steatotic liver disease, even in the presence of worse metabolic dysfunction,” said DiStefano. “The differences in proteins we observed between Black and White women may suggest a protective mechanism.”
The study also found that the INHBE protein was significantly elevated in EVs across all patient groups, including those with severe disease. This finding was further supported by independent hepatic transcriptomic analysis, which demonstrated a progressive increase in INHBE gene expression with worsening disease across the MASLD spectrum, including MASH and liver cirrhosis.
While these findings need further confirmation, “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 relationship between EV protein signatures and increased metabolic dysfunction in postmenopausal women.
The National Institutes of Health/National Cancer institute, NIH/NCI (P30CA33572, U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, U19AG063720, R01127015) funded this research.
Media Contact:
Galen Perry
602-343-8423
gperry@tgen.org
By: Becky Ham | December 16, 2025 | Original Post