Submitted on November 20, 2005
Accepted on June 19, 2006
Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women
Petra Kok1, Ferdinand Roelfsema2, Marijke Frolich3, Johannes van Pelt3, Marcel PM Stokkel4, Edo A Meinders1, and Hanno Pijl2*
1 Dept. of General Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
2 Dept. of Endocrinology and Metabolic diseases, Leiden University Medical Center, Leiden, Netherlands
3 Dept. of Clinical Chemistry, Leiden University Medical Center, Leiden, Netherlands
4 Dept. of Nuclear Medicine, Leiden University Medical Center, Leiden, Netherlands
* To whom correspondence should be addressed. E-mail: h.pijl{at}lumc.nl.
The metabolic syndrome comprises a cluster of metabolic anomalies, including insulin resistance, abdominal obesity, dyslipidemia and hypertension. Previous studies suggest that impaired dopamine D2 receptor (D2R) signalling is involved in its pathogenesis. We studied the acute effects of bromocriptine (a D2R agonist) on energy metabolism in obese women, while body weight and caloric intake remained constant. 18 healthy obese women (BMI 33.2± 0.6 kg/m2, mean age 37.5 ±1.7 range 22-51 years) were studied twice in the follicular phase of their menstrual cycle in a prospective, single blind, design. Subject received both placebo (P) (always 1st occasion) and bromocriptine (B)(always 2nd occasion) on separate occasions for eight days. At each occasion blood glucose and insulin were assessed every 10 minutes during 24 hours and circadian plasma free fatty acids (FFA) and triglyceride (TG) levels were measured hourly. Fuel oxidation was determined by indirect calorimetry. Body weight and -composition were not affected by the drug. Mean 24 h blood glucose (P<0.01) and insulin (P<0.01) were significantly reduced by bromocriptine, whereas mean 24 h FFA levels were increased (P<0.01), suggesting that lipolysis was stimulated. Bromocriptine increased oxygen consumption (P=0.03) and resting energy expenditure (by 50 kCal/day, P=0.03). Systolic blood pressure was significantly reduced by bromocriptine. Thus, these results imply that short term bromocriptine treatment ameliorates various components of the metabolic syndrome, while it shifts energy balance away from lipogenesis in obese humans.
