Apelin Regulates PVN Dopaminergic Activity and Limits Weight Gain in Mice: An Effect Attenuated by High-Fat Diet

Obesity results from an imbalance between calorie intake and expenditure, particularly under a high-fat diet (HFD). Apelin and dopamine may influence food intake and obesity. This study aimed to examine apelin's effect on PVN dopaminergic neurotransmission under standard diet (SD) and HFD using fiber photometry. Thirty-two adult male C57BL/6 mice were randomly assigned to four groups: SD, HFD, SD with apelin (SD + A), and HFD with apelin (HFD + A). Food intake, body weight, blood glucose, and behavioral profiles of the animals were analyzed. PVN dopaminergic activity was measured by fiber photometry using a dopamine sensor, and co-expression of the apelin receptor (APJ) and tyrosine hydroxylase (TH) was examined by double immunofluorescence. The body weights of SD (p < 0.01), HFD (p < 0.001), and HFD + A (p < 0.001) groups on day 28 were significantly higher than day 0. On day 28, the body weight in the SD + A group was lower compared to the HFD and HFD + A (p < 0.001) groups. Apelin did not significantly affect anxiety, exploration, or sociability levels. Fiber photometric dopamine sensor activity results revealed higher dopaminergic activity in the SD + A group compared to the SD (p < 0.05) and HFD + A (p < 0.05) groups. Additionally, co-expression of TH and APJ was observed in PVN neurons. Our study is the first to investigate apelin using fiber photometry and to show that the APJ is expressed in PVN^TH-positive neurons. Apelin regulates PVN dopaminergic signaling and limits weight gain, though these effects are partially attenuated under HFD, potentially through dopaminergic and metabolic pathways. APJ/TH co-expression in PVN suggests a role in homeostatic food intake regulation.