| Full text | |
| Author(s): Show less - |
Pinto, Livia de Fraia
[1]
;
Compri, Cecilia Melleti
[1]
;
Fornari, Joao Victor
[1]
;
Bartchewsky, Waldemar
[1]
;
Cintra, Dennys Eduardo
[2]
;
Trevisan, Miriam
;
Carvalho, Patricia de Oliveira
[1]
;
Ribeiro, Marcelo Lima
[1]
;
Velloso, Licio A.
[2]
;
Saad, Mario J.
[2]
;
Pedrazzoli, Jr., Jose
[1]
;
Gambero, Alessandra
Total Authors: 12
|
| Affiliation: | [1] Univ Sao Francisco, Sch Med, Clin Pharmacol & Gastroenterol Unit, BR-12916900 Braganca Paulista, SP - Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, Campinas, SP - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | LIVER INTERNATIONAL; v. 30, n. 4, p. 603-610, APR 2010. |
| Web of Science Citations: | 22 |
| 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. (AU) | |
| FAPESP's process: | 07/07735-5 - Adipose tissue and inflammation: Role of adipocytokines in the human macrophage differentiation in vitro and immunosuppressant therapy effects on systemic and adipose tissue alterations in diet-inducing obesity in mice. |
| Grantee: | Alessandra Gambero |
| Support Opportunities: | Regular Research Grants |