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

Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy
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;
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.

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.

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.

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