Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet

Abstract Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine...

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Autores principales:	Liliana F. Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M. Yen, Rohit A. Sinha
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4890c10cb2c40409ff2e638a86214b1
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spelling	oai:doaj.org-article:a4890c10cb2c40409ff2e638a86214b12021-12-02T12:32:41ZMetabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet10.1038/s41598-017-02205-12045-2322https://doaj.org/article/a4890c10cb2c40409ff2e638a86214b12017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02205-1https://doaj.org/toc/2045-2322Abstract Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD.Liliana F. IannucciFederica CioffiRosalba SeneseFernando GogliaAntonia LanniPaul M. YenRohit A. SinhaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liliana F. Iannucci Federica Cioffi Rosalba Senese Fernando Goglia Antonia Lanni Paul M. Yen Rohit A. Sinha Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
description	Abstract Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD.
format	article
author	Liliana F. Iannucci Federica Cioffi Rosalba Senese Fernando Goglia Antonia Lanni Paul M. Yen Rohit A. Sinha
author_facet	Liliana F. Iannucci Federica Cioffi Rosalba Senese Fernando Goglia Antonia Lanni Paul M. Yen Rohit A. Sinha
author_sort	Liliana F. Iannucci
title	Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
title_short	Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
title_full	Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
title_fullStr	Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
title_full_unstemmed	Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet
title_sort	metabolomic analysis shows differential hepatic effects of t2 and t3 in rats after short-term feeding with high fat diet
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a4890c10cb2c40409ff2e638a86214b1
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Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet

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