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.

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 (T-2) and triiodothyronine (T-3) 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 T-2 and T-3 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 T-2 and T-3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T-2 and T-3 decreased hepatic fat content, only T-2 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 T-2 and T-3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T-2 and T-3 that also may be important in the prevention and treatment of NAFLD.

Metabolomic analysis shows differential hepatic effects of T-2 and T-3 in rats after short-term feeding with high fat diet

SENESE, Rosalba;GOGLIA, Fernando;LANNI, Antonia;
2017

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 (T-2) and triiodothyronine (T-3) 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 T-2 and T-3 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 T-2 and T-3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T-2 and T-3 decreased hepatic fat content, only T-2 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 T-2 and T-3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T-2 and T-3 that also may be important in the prevention and treatment of NAFLD.
2017
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.
File in questo prodotto:
File Dimensione Formato  
Scientific reports.pdf

accesso aperto

Descrizione: articolo principale
Licenza: Dominio pubblico
Dimensione 1.72 MB
Formato Adobe PDF
1.72 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/375932
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 41
social impact