SEX DIFFERENCES IN EFFECTS OF ILEAL INTERPOSITION SURGERY ON GLUCOSE REGULATION IN MELANOCORTIN-4 RECEPTOR DEFICIENT RATS

We aimed to determine the metabolic differences between male and female rats after ileal interposition surgery and determine whether the remission of insulin resistance after ileal interposition is dependent on melanocortin-4 receptor signaling in both male and female rats. All age-matched male and female rats were treated with either sham or ileal interposition surgery. Glucose tolerance tests and body composition analysis were then performed. Our results indicated a loss of Mc4r function in both male and female rats induced obesity; male knockout rats with sham surgery, not female knockout rats with sham surgery, showed impaired glucose tolerance; insulin resistance of both knockout sham rats and pairfeeding sham rats is significantly higher than that of knockout interposition rats and pairfeeding interposition rats respectively in both male and female rats; interposition surgery decreased both fat percentage and fat mass in female rats, not in male rats, in the long run. In conclusion, Melanocortin-4 Receptor signaling is not necessary for the underlying beneficial effects of ileal interposition on glucose metabolism and insulin resistance. Female rats might get more stable benefits than male rats after the surgery.