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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)....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8657920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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