Suppression of Cytosolic Phospholipase A2 in the Ventromedial Hypothalamus Induces Hyperphagia and Obesity

Background: We recently reported that phospholipase A2 (PLA2)-mediated production of prostaglandins within the ventromedial hypothalamus (VMH) plays a critical role in systemic glucose homeostasis. However, the role of PLA2 in the VMH in regulating food intake is still unclear. Here, we attempted to investigate the role of PLA2 in regulating food intake and body weight. Methods: We injected an adeno-associated virus encoding short hairpin RNA (AAV-shRNA) targeting cytosolic phospholipase A2 (shPla2g4a) into the VMH. We assessed food intake, body weight, oxygen consumption, glucose tolerance, and insulin sensitivity. Results: Three weeks after the AAV injection, the shPla2g4a group increased food intake and body weight gain compared to controls (shSCRM). Energy expenditure, oxygen consumption, and respiratory quotient were comparable between groups. Conclusion: Our findings suggest that the cPLA2-mediated pathway in the VMH is critical for feeding behavior and maintaining energy homeostasis. Further investigation is needed to elucidate the underlying mechanisms.