Efeito do inibidor seletivo da ciclooxigenase do tipo 2 (celecoxibe) sobre as citocinas inflamatórias e o sistema renina-angiotensina no tecido adiposo e sobre a lipogênese na esteatose hepática em modelo murino de obesidade

Abstract

The renin-angiotensin system (RAS) is already recognized as an important modulator of metabolic processes of the body, its activation being the main contributor to obesity / metabolic syndrome associated with pro-inflammatory and liver damage. Thus, activation of this system may be involved in the development of hepatic steatosis with a consequent stimulation of lipogenesis. This study aimed to investigate the effect of oral administration of celecoxib, an anti-inflammatory inhibitor of cyclRooxygenase-2 (ICOX-2), on the reninangiotensin system (RAS) and inflammatory mediators in white adipose tissue, in addition to the action of this drug on lipogenesis in obesity and fatty liver. Mice male FVB / N were divided in 3 groups were fed with the following experimental diets: standard with first (DP); the second high-fat diet (DH), both for four months; and third, which was fed DH during four months, and treated with COX-2 inhibitor (DH + ICOX) for two months at a dosage of 100 mg / kg body weight. They evaluated the body weight and food intake. At first, blood parameters (glucose tolerance, insulin sensitivity, high-density lipoprotein-C, total cholesterol, glucose and triglyceride levels) were evaluated. Real-time PCR was performed in epididymal adipose tissue samples to analyze angiotensinogen expression (AGT), angiotensin-converting enzyme (ACE) inhibitors, interleukin-6 (IL-6) and tumor-α necrosis factor (TNF-α) . In the second stage, histology and expression of ACC, PPAR-γ, FAS, SREBP-1c using real-time polymerase chain reaction (qRT-PCR) were evaluated in the liver. The results showed that selective cyclooxygenase-2 inhibitor (celecoxib) is able to promote weight loss in obese animals considered and reduce food consumption. This work shows differences in mRNA expression levels of ACE, AGT, TNF-α and IL-6 between groups, being lower in the group receiving treatment with celecoxib. Furthermore, ICOX-2 decreased blood glucose and triglyceride levels in animals fed high fat diet. It was also observed, increasing HDL in the treated group. The survey also showed the analysis of genes related to adipogenesis liver, the mRNA expression of ACC, FAS, PPAR γ and SREBP1-C in the liver were suppressed significantly in animals receiving treatment. Therefore, it is concluded that treatment with celecoxib improved lipid metabolism and promoted decrease fat deposition in the liver, in addition to modulate markers of the renin-angiotensin system and lipogenesis. These findings open up a new perspective for the pharmacotherapy of these metabolic disorders (metabolic syndrome / obesity and fatty liver).