Wg. Haynes et al., Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic, HYPERTENSIO, 33(1), 1999, pp. 542-547
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Leptin plays an important role in regulation of body weight through regulat
ion of food intake and sympathetically mediated thermogenesis. The hypothal
amic melanocortin system, via activation of the melanocortin-4 receptor (MC
4-R), decreases appetite and weight, but its effects on sympathetic nerve a
ctivity (SNA) are unknown. In addition, it is not known whether sympathoact
ivation to leptin is mediated by the melanocortin system. We tested the int
eractions between these systems in regulation of brown adipose tissue (BAT)
and renal and lumbar SNA in anesthetized Sprague-Dawley rats. Intracerebro
ventricular administration of the MC4-R agonist MT-II (200 to 600 pmol) pro
duced a dose-dependent sympathoexcitation affecting BAT and renal and lumba
r beds. This response was completely blocked by the MC4-R antagonist SHU911
9 (30 pmol ICV), Administration of leptin (1000 mu g/kg IV) slowly increase
d BAT SNA (baseline, 41+/-6 spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001)
and renal SNA (baseline, 116+/-16 spikes/s; 6 hours, 169+/-26 spikes/s; P=0
.014). Intracerebroventricular administration of SHU9119 did not inhibit le
ptin-induced BAT sympathoexcitation (baseline, 35+/-7 spikes/s; 6 hours, 15
8+/-34 spikes/s; P=0.71 versus leptin alone). However, renal sympathoexcita
tion to leptin was completely blocked by SHU9119 (baseline, 142+/-17 spikes
/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus leptin alone). This study de
monstrates that the hypothalamic melanocortin system can act to increase sy
mpathetic nerve traffic to thermogenic BAT and other tissues. Our data also
suggest that leptin increases renal SNA through activation of hypothalamic
melanocortin receptors. In contrast, sympathoactivation to thermogenic BAT
by leptin appears to be independent of the melanocortin system.