The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice.
Liver Int
; 30(4): 603-10, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20088867
ABSTRACT
BACKGROUND:
Pro-inflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, are known to be involved in the establishment of insulin resistance. Insulin resistance plays a key role in the development of obesity-related pathologies, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The state of chronic inflammation associated with obesity led us to hypothesize that TNF-alpha blockade may have an effect on experimentally obese animals.AIMS:
We studied the effects of thalidomide, an immunosuppressant and anti-TNF-alpha drug, on hepatic alterations that were induced by a high-fat diet (HFD) in mice.METHODS:
Obesity was induced in Swiss mice using a HFD for 12 weeks. Thalidomide-treated animals received thalidomide i.p. (100 mg/kg/day, 10 days). Glucose, aspartate aminotransferases and alanine aminotransferases levels were assessed in the blood. Insulin and glucose tolerance tests were performed. The liver was excised for histological, triglyceride, gene and protein expression analyses.RESULTS:
We found improvements in both the basal glucose blood levels and the response to insulin administration in the treated animals. The molecular analysis of insulin signalling revealed a restoration of the hepatic insulin receptor substrate (IRS)-1 and AKT phosphorylation. The hepatic expression of TNF-alpha was inhibited and the levels correlated with a significant reduction in the steatosis area. Other hepatic inflammatory markers, such as iNOS and suppressor of cytokine signalling (SOCS-3), were also reduced.CONCLUSIONS:
We suggest that immunosuppressant drugs that target TNF-alpha and that may also contribute to reductions in the inflammatory markers that are associated with obesity could be a therapeutic option in NAFLD and type 2 diabetes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Talidomida
/
Gorduras na Dieta
/
Fígado Gorduroso
/
Imunossupressores
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article