Oxytocin stimulates lipolysis, prostaglandin E2 synthesis, and leptin secretion in 3T3-L1 adipocytes

Abstract

A model of oxytocin in the regulation of metabolic status has described one of oxytocin synthesis and release from the neurohypophysis in response to leptin, to suppress further leptin release. In addition, a lipogenic role for oxytocin has been suggested, consistent with an insulinergic action. This model, however, may be incorrect. Oxytocin reduces fat mass in the absence of either leptin or leptin receptor signalling, thereby challenging the interdependence between leptin and oxytocin. An oxytocin induced production of the anti-lipolytic prostaglandin E2 (PGE2) might account for this. Media from 3T3-L1 differentiated adipocytes treated with oxytocin (0–50 nmol.L−1) for 24 hrs were assayed for PGE2, leptin, adiponectin, and glycerol. Harvested cells were analysed for lipid droplet triglyceride and cytosolic free fatty acid (FFA) by flow cytometry, and for altered expression of lipolytic and lipogenic associated gene ontology transcripts by cDNA array. Both PGE2 and leptin secretion were significantly increased by oxytocin treatment whilst adiponectin secretion was not. A significant increase in cytosolic FFA was detected following oxytocin treatment, similar to that determined following treatment with isoproterenol (positive control). A significant increase in glycerol release to the culture media confirmed a lipolytic effect. No enrichment of lipolytic and lipogenic associated gene ontology transcripts was determined, but significant overrepresentation of chemosensory olfactory transcripts was. In conclusion, oxytocin stimulates lipolysis in 3T3-L1 adipocytes, mediated by autocrine/paracrine actions of PGE2 and leptin. To confirm that this response is mediated solely by the oxytocin receptor, further experiments would require those effects being blocked by a specific oxytocin antagonist.