Leptin receptor signaling in is required for normal body POW neurons weight homeostasis

被引:737
作者
Balthasar, N
Coppari, R
McMinn, J
Liu, SM
Lee, CE
Tang, V
Kenny, CD
McGovern, RA
Chua, SC
Elmquist, JK
Lowell, BB
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
[3] Columbia Univ, Dept Pediat, New York, NY 10032 USA
关键词
D O I
10.1016/j.neuron.2004.06.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neuroanatomical and electrophysiological studies have shown that hypothalamic POMC neurons are targets of the adipostatic hormone leptin. However, the physiological relevance of leptin signaling in these neurons has not yet been directly tested. Here, using the Cre/ IoxP system, we critically test the functional importance of leptin action on POMC neurons by deleting leptin receptors specifically from these cells in mice. Mice lacking leptin signaling in POMC neurons are mildly obese, hyperleptinemic, and have altered expression of hypothalamic neuropeptides. In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis.
引用
收藏
页码:983 / 991
页数:9
相关论文
共 57 条
[1]   Role of leptin in the neuroendocrine response to fasting [J].
Ahima, RS ;
Prabakaran, D ;
Mantzoros, C ;
Qu, DQ ;
Lowell, B ;
MaratosFlier, E ;
Flier, JS .
NATURE, 1996, 382 (6588) :250-252
[2]   Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice [J].
Albarado, DC ;
McClaine, J ;
Stephens, JM ;
Mynatt, RL ;
Ye, JP ;
Bannon, AW ;
Richards, WG ;
Butler, AA .
ENDOCRINOLOGY, 2004, 145 (01) :243-252
[3]   STAT3 signalling is required for leptin regulation of energy balance but not reproduction [J].
Bates, SH ;
Stearns, WH ;
Dundon, TA ;
Schubert, M ;
Tso, AWK ;
Wang, YP ;
Banks, AS ;
Lavery, HJ ;
Haq, AK ;
Maratos-Flier, E ;
Neel, BG ;
Schwartz, MW ;
Myers, MG .
NATURE, 2003, 421 (6925) :856-859
[4]   Hyperphagia and weight gain after gold-thioglucose: Relation to hypothalamic neuropeptide Y and proopiomelanocortin [J].
Bergen, HT ;
Mizuno, TM ;
Taylor, J ;
Mobbs, CV .
ENDOCRINOLOGY, 1998, 139 (11) :4483-4488
[5]  
BJORKHOLM JE, 1998, INTEL TECHNOL J Q, V3, P1
[6]   Independent and additive effects of central POMC and leptin pathways on murine obesity [J].
Boston, BA ;
Blaydon, KM ;
Varnerin, J ;
Cone, RD .
SCIENCE, 1997, 278 (5343) :1641-1644
[7]   EVIDENCE THAT BETA-ENDORPHIN IS SYNTHESIZED IN CELLS IN THE NUCLEUS-TRACTUS-SOLITARIUS - DETECTION OF POMC MESSENGER-RNA [J].
BRONSTEIN, DM ;
SCHAFER, MKH ;
WATSON, SJ ;
AKIL, H .
BRAIN RESEARCH, 1992, 587 (02) :269-275
[8]   Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat [J].
Butler, AA ;
Marks, DL ;
Fan, W ;
Kuhn, CM ;
Bartolome, M ;
Cone, RD .
NATURE NEUROSCIENCE, 2001, 4 (06) :605-611
[9]   RECOMBINANT MOUSE OB PROTEIN - EVIDENCE FOR A PERIPHERAL SIGNAL LINKING ADIPOSITY AND CENTRAL NEURAL NETWORKS [J].
CAMPFIELD, LA ;
SMITH, FJ ;
GUISEZ, Y ;
DEVOS, R ;
BURN, P .
SCIENCE, 1995, 269 (5223) :546-549
[10]   NEUROPEPTIDE-Y ADMINISTERED CHRONICALLY INTO THE LATERAL VENTRICLE PROFOUNDLY INHIBITS BOTH THE GONADOTROPIC AND THE SOMATOTROPIC AXIS IN INTACT ADULT FEMALE RATS [J].
CATZEFLIS, C ;
PIERROZ, DD ;
ROHNERJEANRENAUD, F ;
RIVIER, JE ;
SIZONENKO, PC ;
AUBERT, ML .
ENDOCRINOLOGY, 1993, 132 (01) :224-234