Exploring the role of cellular plasticity in metabolic dysfunction-associated steatosis and related molecular mechanisms.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

In chronic diseases, hepatocytes may dedifferentiate and form a liver progenitor cell (LPC)-like population in response to long-term stress stimuli. We investigated the hypothesis that hepatocytes may dedifferentiate upon chronic high insulin stimulation and subsequently form adipocytes and/or fibroblast-like cells as a result of long-term fatty acid exposure. HepG2 cells were treated with prolonged high insulin followed by oleic acid (OA). The expression level of LPC, adipocyte and fibroblast marker genes was measured. Populations of cells carrying the LPC marker CD34, the fibroadipogenic progenitor cell marker PDGFR1α and the activated fibroblast marker FAPα were detected. Lipid accumulation and the existence of the adipocyte marker perilipin-A were shown. The relevant molecular mechanism was investigated by applying specific inhibitors and determining related protein levels. With high insulin exposure, the number of CD34 + or PDGFR1α + cells and the gene expression levels of LPC markers increased, whereas the gene expression of hepatocyte markers decreased. Lipid accumulation, adipogenesis and adipocyte marker gene expression levels and the density of Perilipin-A increased in cells treated with OA following high insulin. On the other hand, in cells treated with OA alone or OA following insulin, the expression levels of fibroblast marker genes and the FAPα + cell population w

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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