Investigation of the effects of systemic apelin administration on appetite regulation in diabetic AGRP transgenic mice

Diabetes has become an increasingly common public health problem in recent years. The causes of type 2 diabetes (T2D) include insulin resistance developing as a result of overweight and obesity caused by mainly due to sedentary life and overeating, and less frequently aging and genetic factors, while T1D is mainly caused by the autoimmune destruction of insulin-producing beta cells. Energy homeostasis is maintained by orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) and anorexigenic proopiomelanocortin/cocaine-amphetamine-associated transcript (POMC/CART) neurons in the hypothalamic arcuate nucleus (ARC), and peripheral inputs. Apelin is an adipokine having different physiological roles including blood glucose regulation. In our study, we aimed to examine the effects of systemic apelin administration on food intake, hyperglycemia and AgRP neuronal activity in streptozotocin (STZ)-induced diabetes in transgenic mice. Following the stereotaxic AAV-CAG-Flex-GFP injection by targeting ARC in young adult AgRP-Ires-Cre animals, they were administered STZ and/or apelin, and their food intake, body weight and blood glucose were monitored. On the sacrification day, serum was collected for ELISA measurements and brain slices were obtained to examine the electrophysiological activities of AgRP neurons. While food intake decreased significantly during STZ administration, it started to increase in the post-STZ period. Administration of 50 mg/kg apelin reduced food intake and body weight in animals independent of STZ. Food intake continued to increase significantly after discontinuation of STZ at 100 mg/kg apelin administration and long-term follow-up after apelin. Apelin did not affect STZ-induced increase in blood glucose and decreased serum insulin levels. Serum triglyceride levels elevated after STZ administration significantly decreased after 100 mg/kg apelin administration. While apelin did not change AgRP neuronal activity, STZ increased it significantly. Apelin, on the other hand, tended to decrease STZ-induced AgRP neuronal activity. These results suggest that apelin does not affect the increase in AgRP neuron activity caused by diabetes.