TY - JOUR
T1 - Systemic administration of leptin decreases plasma corticosterone levels: role of hypothalamic norepinephrine.
T2 - Role of hypothalamic norepinephrine
AU - Clark, K A
AU - Shin, Andrew
AU - Sirivelu, M P
AU - Mohankumar, S M
AU - Mohankumar, P S
N1 - Funding Information:
This study was supported in part by NSF IBN 0236385 to SMJM and PSM and NIH AG 027697 to PSM and SMJM. Andrew Shin was supported by the Biomedical Health Research Initiative funds, MSU. We would like to thank Ms. Katrina Linning for technical assistance.
PY - 2008/2/21
Y1 - 2008/2/21
N2 - Leptin, an adipocyte-derived hormone, is known to regulate a variety of neuroendocrine functions. It inhibits the hypothalamo-pituitary-adrenal axis (HPA) in several animal models, however, the exact mechanism by which it does so is not known. Since norepinephrine (NE) is a key regulator of the HPA axis, we hypothesized that leptin could suppress HPA activity by decreasing NE levels. To study this, we implanted adult male Sprague-Dawley rats with both a push-pull cannula in the paraventricular nucleus (PVN) and a catheter in the jugular vein. Animals were treated with either 0 or 100 μg or 500 μg of recombinant rat leptin (Lep). Push-pull perfusion was performed from 1000-1600 h. Perfusate samples were collected every 30 min and analyzed for NE levels using HPLC-EC. Blood samples were collected every 60 min and analyzed for corticosterone (CS) levels. To further understand the role of NE in this phenomenon animals were treated with either an α1-adrenergic agonist, phenylephrine (PHE; 0.5 mg/kg BW), an α2-adrenergic agonist, clonidine (CLON; 0.6 mg/kg BW), or a β-adrenergic agonist, isoproterenol (ISO; 0.2 mg/kg BW) alone or in combination with 500 μg of Lep. Pre-treatment and hourly post-treatment blood samples were collected, plasma was separated and analyzed for CS levels. Leptin administration decreased NE release in the PVN significantly by 30 min (p < 0.05). It also significantly reduced plasma CS levels at 240 and 300 min (p < 0.05). Administration of either PHE or CLON in combination with leptin prevented the leptin-induced decrease in CS. In contrast, administration of ISO along with leptin did not prevent the leptin-induced decrease in CS. These results indicate that leptin decreases hypothalamic NE and plasma CS and that this effect is most probably mediated through alpha-adrenergic receptors.
AB - Leptin, an adipocyte-derived hormone, is known to regulate a variety of neuroendocrine functions. It inhibits the hypothalamo-pituitary-adrenal axis (HPA) in several animal models, however, the exact mechanism by which it does so is not known. Since norepinephrine (NE) is a key regulator of the HPA axis, we hypothesized that leptin could suppress HPA activity by decreasing NE levels. To study this, we implanted adult male Sprague-Dawley rats with both a push-pull cannula in the paraventricular nucleus (PVN) and a catheter in the jugular vein. Animals were treated with either 0 or 100 μg or 500 μg of recombinant rat leptin (Lep). Push-pull perfusion was performed from 1000-1600 h. Perfusate samples were collected every 30 min and analyzed for NE levels using HPLC-EC. Blood samples were collected every 60 min and analyzed for corticosterone (CS) levels. To further understand the role of NE in this phenomenon animals were treated with either an α1-adrenergic agonist, phenylephrine (PHE; 0.5 mg/kg BW), an α2-adrenergic agonist, clonidine (CLON; 0.6 mg/kg BW), or a β-adrenergic agonist, isoproterenol (ISO; 0.2 mg/kg BW) alone or in combination with 500 μg of Lep. Pre-treatment and hourly post-treatment blood samples were collected, plasma was separated and analyzed for CS levels. Leptin administration decreased NE release in the PVN significantly by 30 min (p < 0.05). It also significantly reduced plasma CS levels at 240 and 300 min (p < 0.05). Administration of either PHE or CLON in combination with leptin prevented the leptin-induced decrease in CS. In contrast, administration of ISO along with leptin did not prevent the leptin-induced decrease in CS. These results indicate that leptin decreases hypothalamic NE and plasma CS and that this effect is most probably mediated through alpha-adrenergic receptors.
KW - Corticosterone
KW - Hypothalamus
KW - Leptin
KW - Norepinephrine
KW - Paraventricular nucleus
UR - http://www.scopus.com/inward/record.url?scp=39149121809&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2007.12.009
DO - 10.1016/j.brainres.2007.12.009
M3 - Article
C2 - 18191822
SN - 0006-8993
VL - 1195
SP - 89
EP - 95
JO - Brain Research
JF - Brain Research
ER -