Decreased mitogen response of splenic lymphocytes in obese Zucker rats is associated with the decreased expression of glucose transporter 1 (GLUT-1)

We reported previously that obesity is a risk factor for deteriorating cellular immune functions in aging. However, the mechanism by which obesity decreases cellular immunity remains to be elucidated. To determine the mechanism of the decrease in cellular immunity with obesity, lean (Fa/?) and obese (fa/fa) 12-mo-old Zucker rats were used. The mitogen response of splenic lymphocytes in obese Zucker rats was significantly lower than that of lean Zucker rats, which was not restored by in vitro treatment with indomethacin (10 mu mol/L), an inhibitor of prostaglandin E-2 (PGE(2)), In addition, PGE(2) production by splenic lymphocytes was not greater in obese than in lean Zucker rats. Glucose consumption by splenic lymphocytes after in vitro incubation with concanavalin A (conA) for 48 h was also significantly lower in obese Zucker rats. Expression of glucose transporter 1 (GLUT-I), analyzed by Western blot analysis, was lower in splenic lymphocytes of obese than in lean Zucker rats. However, the expression of the conA receptor in splenic lymphocytes, analyzed by flow cytometry with fluorescein isothiocyanate-conjugated conA, was not significantly different between lean and obese Zucker rats. In conclusion, the decreased mitogen response of splenic lymphocytes in obese Zucker rats may be due in part to the decreased uptake of glucose as the main energy source for lymphocytes at the stage of proliferation and may be associated with the decreased expression of GLUT-1.