Activation of dopamine D2 receptors lowers circadian leptin concentrations in obese women

Context: Leptin release is regulated by factors other than fat mass alone. Previous observations provide indirect evidence for an inhibitory effect of dopaminergic neurotransmission on leptin secretion. This study was done to establish the effect of bromocriptine treatment on circadian plasma leptin concentrations in obese humans. Objective: The objective of the study was to study the acute effects of bromocriptine (a D2R agonist) on circadian leptin levels in obese women, whereas body weight and caloric intake remained constant. Design: This was a prospective, single-blind, crossover study (2004). Setting: The study was conducted at a clinical research center. Participants: Eighteen healthy obese women (body mass index 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle. Intervention(s): Treatment consisted of bromocriptine or placebo for 8 d. Main Outcome Measure(s): Blood was collected during 24 h at 20-min intervals for determination of leptin concentrations at the last day of medical treatment (bromocriptine or placebo). Mean 24-h serum concentrations were determined for insulin, glucose, free fatty acids, and triglycerides. Results: Short-term treatment with bromocriptine reduced leptin concentration (placebo 33.6 +/- 2.5 vs. bromocriptine 30.5 +/- 2.5 ng/liter, P = 0.03). Free fatty acid concentrations were increased by treatment with bromocriptine. The increase of free fatty acids was inversely related with the decline of leptin levels. The decline of glucose, insulin, or prolactin concentrations in response to bromocriptine was not correlated with the reduction of leptin. Conclusion: Activation of dopamine D2 receptors by bromocriptine lowers circulating leptin levels in obese women, which suggests that dopaminergic neurotransmission is involved in the control of leptin release in humans.