Models of non-Alcoholic Fatty Liver Disease and Potential Translational Value: the Effects of 3,5-L-diiodothyronine.
Ann Hepatol
; 16(5): 707-719, 2017.
Article
em En
| MEDLINE
| ID: mdl-28809727
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD. Liver steatosis was invariably associated with increased number/size of lipid droplets (LDs) and modulation of expression of genes coding for key genes of lipid metabolism such as peroxisome proliferator-activated receptors (Ppars) and perilipins (Plins). In these models, we tested the anti-steatotic effects of 3,5-L-diiodothyronine (T2), a metabolite of thyroid hormones. T2 markedly reduced triglyceride content and LD size acting on mRNA expression of both Ppars and Plins. T2 also stimulated mitochondrial oxidative metabolism of fatty acids. We conclude that in vivo and especially in vitro models of NAFLD are valuable tools to screen a large number of compounds counteracting the deleterious effect of liver steatosis. Because of the high and negative impact of liver steatosis on human health, ongoing experimental studies from our group are unravelling the ultimate translational value of such cellular models of NAFLD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatócitos
/
Di-Iodotironinas
/
Hepatopatia Gordurosa não Alcoólica
/
Fígado
Tipo de estudo:
Etiology_studies
Aspecto:
Patient_preference
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Ann Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article