Efeitos da ausência do baço sobre a homeostase glicêmica de ratos machos Wistar obesos e não obesos

Abstract

Obesity is characterized by an excess of white adipose tissue (WAT) which promotes low-level chronic inflammation, closely related to glucose intolerance and insulin resistance (IR). The spleen, due to immunological actions, seems to influence glycemic homeostasis, modifying the endocrine pancreas and insulin sensitivity. The present study evaluated the effect of spleen removal on glycemic homeostasis in non-obese and obese male Wistar rats. Hypothalamic obesity was induced by subcutaneous administration of monosodium glutamate (MSG; 4g / kg) in the first five days of life. In the same period, Control animals (CON) received equimolar saline. MSG and CON rats were randomly divided into subgroups, separated according to the splenectomy phase (SPL), which occurred at 21 or 60 days of life, forming the CON-SPL21 groups; CON-SPL60; MSG-SPL21 and MSG-SPL60 (n = 14 rats / group). False-operated animals (FO) served as surgical controls (CON-FO and MSG-FO). Food intake and body weight were monitored at 70-90 days of life, and food efficiency was calculated. At 90 days the rats were subjected to an intravenous glucose tolerance test (ivGTT; 1g / kg) and an insulin test (II), a calculated IR measurement. In euthanasia (90 days), body weight, the depots of WAT, Inguinal (WAT-I) and Retroperitoneal (WAT-R) and isolated pancreatic islets were evaluated for the study of insulin secretion induced by glucose (GIIS) and expression of Glucose transporters of subtype 2 (GLUT-2) and Glucokinase (GCK). MSG rats showed lower body weight and growth besides greater adiposity, accompanied by dyslipidemia, glucose intolerance and IR compared to CON rats. Despite the higher food intake in the CON-SPL21 group, the body weight gain of the CON-SPL21 and CON-SPL60 animals was significantly lower compared to the CON-FO animals, resulting in lower feed efficiency. Glucose tolerance was lower in CON-SPL21 rats than in animals CON-FO and CON-SPL60, without changing the IR; insulinemia or GIIS. However, total cholesterol was reduced in the CON-SPL21 group compared to the CON-FO animals (p <0.05). MSG-SPL21 showed greater weight gain while MSGSPL60 animals showed a decrease in weight gain compared to FO rats. Regardless of the stage of life, splenectomy reduced insulin during ivGTT in MSG animals, but only after 21 days did blood glucose fall, while MSG-SPL60 showed greater sensitivity to insulin compared to the MSG-FO group (p <0.05). Additionally, GIIS was significantly lower in islets of MSG-SPL21 rats compared to islets of MSG-FO rats (p <0.05) and there was an increase in GCK expression in islets of the MSG-SPL60 group when compared to the MSG-FO group. and MSG-SPL21 but did not modify the expression of GLUT-2. In conclusion, splenectomy reduces body weight in nonobese rats, despite hyperphagia, suggesting high energy expenditure. On the other hand, in conditions of MSG-induced obesity, removal of the spleen corrected glucose tolerance and reduced insulin secretion, improving insulin sensitivity, indicating that the spleen influences glucose homeostasis in conditions of obesity.