title: Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women.
abstract: 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) signaling is involved in its pathogenesis. We studied the acute effects of bromocriptine (a D2R agonist) on energy metabolism in obese women; body weight and caloric intake remained constant. Eighteen healthy, obese women (BMI 33.2 +/- 0.6 kg/m(2), mean age 37.5 +/- 1.7, range 22-51 yr) were studied twice in the follicular phase of their menstrual cycle in a prospective, single-blind, crossover design. Subjects received both placebo (P; always first occasion) and bromocriptine (B; always second occasion) on separate occasions for 8 days. At each occasion blood glucose and insulin were assessed every 10 min for 24 h, and circadian plasma free fatty acid (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.
authors.affiliation: Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Kok
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: Johannes
authors.initials: J
authors.lastname: van Pelt
authors.forename: Marcel P M
authors.initials: MP
authors.lastname: Stokkel
authors.forename: A Edo
authors.initials: AE
authors.lastname: Meinders
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001971:Bromocriptine / Q000008:administration & dosage*; D002153:Calorimetry, Indirect; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism; D008875:Middle Aged; D009584:Nitrogen / Q000652:urine; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014508:Urea / Q000652:urine
chemical_list: D001786:Blood Glucose; D018491:Dopamine Agonists; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D014508:Urea; D011388:Prolactin; D009584:Nitrogen