The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice.

Autor: Pinto Lde F; Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil., Compri CM, Fornari JV, Bartchewsky W, Cintra DE, Trevisan M, Carvalho Pde O, Ribeiro ML, Velloso LA, Saad MJ, Pedrazzoli J Jr, Gambero A
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2010 Apr; Vol. 30 (4), pp. 603-10. Date of Electronic Publication: 2010 Jan 15.
DOI: 10.1111/j.1478-3231.2009.02200.x
Abstrakt: 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.
Databáze: MEDLINE
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