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<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of chronic liver disease in industrialised countries and is closely related to metabolic syndrome. Several studies have identified a key role of thyroid hormones in regulating hepatic lipid and glucose metabolism, as well as in the inflammatory and fibrotic processes that drive disease progression toward the more advanced metabolic dysfunction-associated steatohepatitis (MASH). The identification of thyroid hormone receptor beta (THR-<InlineEquation ID="IEq6"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40619_2025_1713_Article_IEq1.gif" Format="GIF" Height="17" Rendition="HTML" Resolution="72" Type="Linedraw" Width="15" /> </InlineMediaObject> <EquationSource Format="MATHML"><math> <mi>β</mi> </math></EquationSource> <EquationSource Format="TEX">$\beta $</EquationSource> </InlineEquation>) as a major mediator of the metabolic effects led to the development of selective agonists (thyromimetics) capable of exerting a targeted hepatic action while avoiding the systemic side effects typically associated with activation of the alpha receptor (THR-<InlineEquation ID="IEq7"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="40619_2025_1713_Article_IEq5.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="14" /> </InlineMediaObject> <EquationSource Format="MATHML"><math> <mi>α</mi> </math></EquationSource> <EquationSource Format="TEX">$\alpha $</EquationSource> </InlineEquation>). Among these, resmetirom, recently approved by the Food and Drug Administration (FDA) for the treatment of MASH with moderate-to-advanced fibrosis, and VK2809, currently undergoing clinical trials, have shown promising results in terms of reducing steatosis and fibrosis, as well as improving lipid profile. This review aims to analyse the mechanisms of action, pharmacological characteristics, and the most relevant clinical evidence on thyromimetics, outlining their potential role in the management of metabolic liver disease and future therapeutic perspectives.</p>

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Agonisti selettivi del recettore \(\beta \) degli ormoni tiroidei nel trattamento dell’epatopatia cronica su base dismetabolica

  • 期刊论文

  • 发表日期：

    2025年10月22日

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  • Giordano Paolucci,
  • Alessio Basolo,
  • Paola Fierabracci,
  • Ferruccio Santini

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of chronic liver disease in industrialised countries and is closely related to metabolic syndrome. Several studies have identified a key role of thyroid hormones in regulating hepatic lipid and glucose metabolism, as well as in the inflammatory and fibrotic processes that drive disease progression toward the more advanced metabolic dysfunction-associated steatohepatitis (MASH). The identification of thyroid hormone receptor beta (THR- β $\beta $ ) as a major mediator of the metabolic effects led to the development of selective agonists (thyromimetics) capable of exerting a targeted hepatic action while avoiding the systemic side effects typically associated with activation of the alpha receptor (THR- α $\alpha $ ). Among these, resmetirom, recently approved by the Food and Drug Administration (FDA) for the treatment of MASH with moderate-to-advanced fibrosis, and VK2809, currently undergoing clinical trials, have shown promising results in terms of reducing steatosis and fibrosis, as well as improving lipid profile. This review aims to analyse the mechanisms of action, pharmacological characteristics, and the most relevant clinical evidence on thyromimetics, outlining their potential role in the management of metabolic liver disease and future therapeutic perspectives.