Thyroid hormones as a disease modifier and therapeutic target in nonalcoholic steatohepatitis.
Expert Rev Endocrinol Metab
; 17(5): 425-434, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35957531
ABSTRACT
INTRODUCTION:
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and closely interconnected to the metabolic syndrome. Liver-specific and systemic signaling pathways orchestrating glucose and fatty acid metabolism contribute to intrahepatic accumulation of lipids and inflammatory processes eventually causing disease progression to nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Since a high number of key regulatory genes regarding liver homeostasis are directly mediated via thyroid hormone (TH) signaling, targeting TH receptors (TRs) represent a promising therapeutic potential for the treatment of NAFLD. AREAS COVERED In this review, we elucidate the effects of TH on metabolic regulations in the liver via local availability and actions. We discuss recent advances and the potential impact of thyromimetics in basic research and clinical trials including liver-targeted and TRß-specific agents for the treatment of NAFLD. EXPERT OPINION Unselective TR targeting can be accompanied by negative side effects due to high TRß expression in other organs and TRα-mediated effects. Recent advances in drug development and the introduction of liver-targeted thyromimetics selectively activating TRß such as Resmetirom (MGL-3196) and VK2809 bring new hope of translating the knowledge on local TH effects into effective hepatic lipid-clearing therapies against NASH.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome Metabólica
/
Hepatopatia Gordurosa não Alcoólica
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article