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Article

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

1
Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy
2
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
*
Authors to whom correspondence should be addressed.
Academic Editors: Mariapia Vairetti, Giuseppe Colucci and Andrea Ferrigno
Int. J. Mol. Sci. 2021, 22(23), 13105; https://doi.org/10.3390/ijms222313105
Received: 22 October 2021 / Revised: 29 November 2021 / Accepted: 1 December 2021 / Published: 3 December 2021
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. View Full-Text
Keywords: thyromimetics; steatosis; triglycerides; Resmetirom; NASH; MAFLD thyromimetics; steatosis; triglycerides; Resmetirom; NASH; MAFLD
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MDPI and ACS Style

Caddeo, A.; Kowalik, M.A.; Serra, M.; Runfola, M.; Bacci, A.; Rapposelli, S.; Columbano, A.; Perra, A. TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD. Int. J. Mol. Sci. 2021, 22, 13105. https://doi.org/10.3390/ijms222313105

AMA Style

Caddeo A, Kowalik MA, Serra M, Runfola M, Bacci A, Rapposelli S, Columbano A, Perra A. TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD. International Journal of Molecular Sciences. 2021; 22(23):13105. https://doi.org/10.3390/ijms222313105

Chicago/Turabian Style

Caddeo, Andrea, Marta A. Kowalik, Marina Serra, Massimiliano Runfola, Andrea Bacci, Simona Rapposelli, Amedeo Columbano, and Andrea Perra. 2021. "TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD" International Journal of Molecular Sciences 22, no. 23: 13105. https://doi.org/10.3390/ijms222313105

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