Researchers affiliated with the Perelman School of Medicine at the University of Pennsylvania have determined that excessive cholesterol levels can cause liver tissue to stiffen during the initial phases of MASLD. This study, detailed in the journal PNAS, suggests promising new avenues for both identifying and managing this condition.
The detrimental effects of surplus cholesterol on the liver can manifest in unforeseen ways. Scientists from the Perelman School of Medicine at the University of Pennsylvania found that cholesterol crystals possess the ability to “harden” hepatic tissue in the early stages of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), preceding the onset of scar formation. The findings of this research were published in the Proceedings of the National Academy of Sciences (PNAS).
MASLD progression is linked to fat accumulation in the liver and its incidence is rising, particularly among individuals struggling with obesity, insulin resistance, and type 2 diabetes. During animal trials, experts contrasted the outcomes of high-fat diets with those of diets enriched with both high fats and high cholesterol. While both dietary regimes resulted in hepatic fat buildup, it was specifically the cholesterol surplus that triggered the formation of crystals within the cells. These structures resulted in a greater rigidity of the liver tissue, an effect observed independently of any existing fibrosis.
The study’s authors posit that this increased tissue stiffness contributes to further damage and hastens the fibrotic process. When these crystals were experimentally eliminated, a reduction in liver stiffness was observed, suggesting that this effect might be reversible. However, at present, detecting these specific changes necessitates a liver biopsy.
The research team is optimistic that non-invasive diagnostic tools can eventually be engineered to assess this crystal accumulation. Furthermore, they aim to investigate whether established pharmaceuticals, such as statins, can mitigate the build-up of cholesterol crystals in the liver. Achieving this would open the door for therapeutic intervention at an earlier stage, thereby slowing the advance of the disease.
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