Receptor-mediated regional sympathetic nerve activation by leptin

被引:821
作者
Haynes, WG
Morgan, DA
Walsh, SA
Mark, AL
Sivitz, WI
机构
[1] VET AFFAIRS MED CTR,IOWA CITY,IA 52242
[2] UNIV IOWA,COLL MED,CTR CARDIOVASC,DIABET ENDOCRINE RES CTR,HYPERTENS GENET SPECIALI,IOWA CITY,IA 52242
关键词
autonomic nervous system; renal; neural; thermogenic tissues; obesity;
D O I
10.1172/JCI119532
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure, Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known, We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Dawley rats. Intravenous infusion of mouse leptin over 3 h (total dose 10-1,000 mu g/kg) increased plasma concentrations of immunoreactive murine leptin up to 50-fold. Leptin slowly increased sympathetic nerve activity to brown adipose tissue (+286+/-64% at 1,000 mu g/kg; P = 0.002). Surprisingly, leptin infusion also produced gradual increases in renal sympathetic nerve activity (+228+/-63% at 1,000 mu g/kg; P = 0.0008). The effect of leptin on sympathetic nerve activity was dose dependent, with a threshold dose of 100 mu g/kg. Leptin also increased sympathetic nerve activity to the hindlimb (+287+/-60%) and adrenal gland (388+/-171%), Despite the increase in overall sympathetic nerve activity, leptin did not increase arterial pressure or heart rate, Leptin did not change plasma glucose and insulin concentrations, Infusion of vehicle did not alter sympathetic nerve activity, Obese Zucker rats, known to possess a mutation in the gene for the leptin receptor, were resistant to the sympathoexcitatory effects of leptin, despite higher achieved plasma leptin concentrations, These data demonstrate that leptin increases thermogenic sympathetic nerve activity and reveal an unexpected stimulatory effect of leptin on overall sympathetic nerve traffic.
引用
收藏
页码:270 / 278
页数:9
相关论文
共 29 条
[11]  
DIBONA GF, 1989, AM J HYPERTENS, V2, pA119
[12]   Human blood-brain barrier leptin receptor - Binding and endocytosis in isolated human brain microvessels [J].
Golden, PL ;
Maccagnan, TJ ;
Pardridge, WM .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (01) :14-18
[13]   SYMPATHETIC ACTIVATION IN OBESE NORMOTENSIVE SUBJECTS [J].
GRASSI, G ;
SERAVALLE, G ;
CATTANEO, BM ;
BOLLA, GB ;
LANFRANCHI, A ;
COLOMBO, M ;
GIANNATTASIO, C ;
BRUNANI, A ;
CAVAGNINI, F ;
MANCIA, G .
HYPERTENSION, 1995, 25 (04) :560-563
[14]   WEIGHT-REDUCING EFFECTS OF THE PLASMA-PROTEIN ENCODED BY THE OBESE GENE [J].
HALAAS, JL ;
GAJIWALA, KS ;
MAFFEI, M ;
COHEN, SL ;
CHAIT, BT ;
RABINOWITZ, D ;
LALLONE, RL ;
BURLEY, SK ;
FRIEDMAN, JM .
SCIENCE, 1995, 269 (5223) :543-546
[15]   EFFECT OF CHRONIC HYPERTENSION AND SYMPATHETIC DENERVATION ON WALL-LUMEN RATIO OF CEREBRAL VESSELS [J].
HART, MN ;
HEISTAD, DD ;
BRODY, MJ .
HYPERTENSION, 1980, 2 (04) :419-423
[16]  
Jackson Edwin K., 1996, Hypertension (Dallas), V28, P517
[17]   BODY-WEIGHT AND MORTALITY AMONG WOMEN [J].
MANSON, JE ;
WILLETT, WC ;
STAMPFER, MJ ;
COLDITZ, GA ;
HUNTER, DJ ;
HANKINSON, SE ;
HENNEKENS, CH ;
SPEIZER, FE .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (11) :677-685
[18]   NONUNIFORM REGIONAL SYMPATHETIC-NERVE RESPONSES TO HYPERINSULINEMIA IN RATS [J].
MORGAN, DA ;
BALON, TW ;
GINSBERG, BH ;
MARK, AL .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (02) :R423-R427
[19]  
MORGAN DA, 1988, FASEB J, V2, pA1690
[20]   RENAL SYMPATHETIC-NERVE ACTIVITY IS INCREASED IN OBESE ZUCKER RATS [J].
MORGAN, DA ;
ANDERSON, EA ;
MARK, AL .
HYPERTENSION, 1995, 25 (04) :834-838