Bromocriptine Reduces Obesity, Glucose Intolerance and Extracellular Monoamine Metabolite Levels in the Ventromedial Hypothalamus of Syrian Hamsters

Abstract

We examined whether reductions in body fat stores and insulin resistance in Syrian hamsters induced by bromocriptine are associated with reductions in daily norepinephrine (NE) and serotonin activities as indicated by their extracellular metabolite levels in the ventromedial hypothalamus (VMH). High levels of these monoamines within the VMH have been suspected to induce obesity and insulin resistance. Microdialysate samples from the VMH of freely moving obese male hamsters (BW: 208 ± 5 g) were collected hourly over a 25-hour period before bromocriptine treatment, during the first day of and after 2 weeks of bromocriptine treatment (800 µg/animal daily, i.p.), and body composition and glucose tolerance analyses were conducted before and after 2 weeks of treatments. The microdialysate samples were analyzed by HPLC for metabolites of serotonin: 5-hydroxy-indoleacetic acid (5-HIAA), NE: 3-methoxy-4-hydroxy-phenylglycol (MHPG), and dopamine: homovanillic acid (HVA). Bromocriptine treatment for 14 days significantly reduced body fat by 60% and areas under the glucose and insulin curves during a glucose tolerance test by 50 and 46%, respectively. Concurrently, extracellular VMH contents of 5-HIAA, MHPG, and HVA were reduced by 50, 29 and 66%, respectively (p < 0.05). Similarly, VMH 5-HIAA and MHPG contents were 48 and 44% less, respectively (p < 0.05), in naturally glucose-tolerant hamsters compared with naturally glucose-intolerant hamsters. Bromocriptine induced reductions of body fat, and improvements in glucose intolerance may result in part from its ability to decrease serotonin and NE activities in the VMH.

Effects of Ovariectomy and 17&lt;i&gt;β&lt;/i&gt;-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

“…However, D2 receptors involvement in sucrose intake was not elucidated. On the one hand, previous studies reported that systemic [60] [61] [62] and intracerebral [63] bromocriptine administration in insulin-resistant animals, declined hepatic glucose production and gluconeogenesis, reduced adipose tissue lipolysis, and improved insulin sensitivity [43]. On the other hand, Hajnal et al [15] reported that D2 receptors were involved in heightened sucrose intake observed in the OLETF obese rat.…”

Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine

“…This treatment not only normalized hyperphagia but redirected several metabolic and endocrine activities independent of its effects on feeding to improve the obese/diabetic syndrome in Ob/Ob mice. Furthermore, a study (13) where the authors examined whether reduction in body fat stores and insulin resistance in Syrian hamsters induced by BC were associated with reductions in daily norepinephrine and serotonin activities showed that BC, a potent dopamine D2 agonist, was effective in decreasing elevated noradrenergic and serotonergic activities centrally within the vetromedial hypothalamus. BC treatment of Syrian hamsters for 2 weeks significantly reduced body fat by 60% and areas under the glucose and insulin curves during glucose tolerance test by 50 and 46% respectively.…”

Quantitative Expression Analysis of Genes Regulated by Both Obesity and Leptin Reveals a Regulatory Loop between Leptin and Pituitary-derived ACTH

“…Paradoxically, bromocryptine reduces both prolactin and body weight in obese patients (48). As bromocryptine also modulates seratonin and norepinephrine within the hypothalamus (49), the effects on obesity may be mediated through central rather than peripheral mechanisms.…”