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TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD

Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD)....

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Autores principales: Caddeo, Andrea, Kowalik, Marta Anna, Serra, Marina, Runfola, Massimiliano, Bacci, Andrea, Rapposelli, Simona, Columbano, Amedeo, Perra, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657920/
https://www.ncbi.nlm.nih.gov/pubmed/34884910
http://dx.doi.org/10.3390/ijms222313105
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author Caddeo, Andrea
Kowalik, Marta Anna
Serra, Marina
Runfola, Massimiliano
Bacci, Andrea
Rapposelli, Simona
Columbano, Amedeo
Perra, Andrea
author_facet Caddeo, Andrea
Kowalik, Marta Anna
Serra, Marina
Runfola, Massimiliano
Bacci, Andrea
Rapposelli, Simona
Columbano, Amedeo
Perra, Andrea
author_sort Caddeo, Andrea
collection PubMed
description Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD). C57BL/6 mice fed HFD for 17 or 18 weeks, a time when all mice developed massive steatohepatitis, were then given TG68 at a dose of 9.35 or 2.8 mg/kg for 2 or 3 weeks, respectively. As a reference compound, the same treatment was adopted using equimolar doses of MGL-3196, a selective THRβ agonist currently in clinical phase III. The results showed that treatment with TG68 led to a reduction in liver weight, hepatic steatosis, serum transaminases, and circulating triglycerides. qRT-PCR analyses demonstrated activation of THRβ, as confirmed by increased mRNA levels of Deiodinase-1 and Malic enzyme-1, and changes in lipid metabolism, as revealed by increased expression of Acyl-CoA Oxidase-1 and Carnitine palmitoyltransferase-1. The present results showed that this novel THRβ agonist exerts an anti-steatogenic effect coupled with amelioration of liver injury in the absence of extra-hepatic side effects, suggesting that TG68 may represent a useful tool for the treatment of NAFLD.
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spelling pubmed-86579202021-12-10 TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD Caddeo, Andrea Kowalik, Marta Anna Serra, Marina Runfola, Massimiliano Bacci, Andrea Rapposelli, Simona Columbano, Amedeo Perra, Andrea Int J Mol Sci Article Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD). C57BL/6 mice fed HFD for 17 or 18 weeks, a time when all mice developed massive steatohepatitis, were then given TG68 at a dose of 9.35 or 2.8 mg/kg for 2 or 3 weeks, respectively. As a reference compound, the same treatment was adopted using equimolar doses of MGL-3196, a selective THRβ agonist currently in clinical phase III. The results showed that treatment with TG68 led to a reduction in liver weight, hepatic steatosis, serum transaminases, and circulating triglycerides. qRT-PCR analyses demonstrated activation of THRβ, as confirmed by increased mRNA levels of Deiodinase-1 and Malic enzyme-1, and changes in lipid metabolism, as revealed by increased expression of Acyl-CoA Oxidase-1 and Carnitine palmitoyltransferase-1. The present results showed that this novel THRβ agonist exerts an anti-steatogenic effect coupled with amelioration of liver injury in the absence of extra-hepatic side effects, suggesting that TG68 may represent a useful tool for the treatment of NAFLD. MDPI 2021-12-03 /pmc/articles/PMC8657920/ /pubmed/34884910 http://dx.doi.org/10.3390/ijms222313105 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caddeo, Andrea
Kowalik, Marta Anna
Serra, Marina
Runfola, Massimiliano
Bacci, Andrea
Rapposelli, Simona
Columbano, Amedeo
Perra, Andrea
TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title_full TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title_fullStr TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title_full_unstemmed TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title_short TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
title_sort tg68, a novel thyroid hormone receptor-β agonist for the treatment of nafld
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657920/
https://www.ncbi.nlm.nih.gov/pubmed/34884910
http://dx.doi.org/10.3390/ijms222313105
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