Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons.
Acute leptin administration results in a depolarization and concomitant increase in the firing rate of a subpopulation of arcuate proopiomelanocortin (POMC) cells. This rapid activation of POMC cells has been implicated as a cellular correlate of leptin effects on energy balance. In contrast to leptin, insulin inhibits the activity of some POMC neurons. Several studies have described a "cross talk" between leptin and insulin within the mediobasal hypothalamus via the intracellular enzyme, phosphoinositol-3-kinase (PI3K). Interestingly, both insulin and leptin regulate POMC cellular activity by activation of PI3K; however, it is unclear whether leptin and insulin effects are observed in similar or distinct populations of POMC cells. We therefore used dual label immunohistochemistry/in situ hybridization and whole-cell patch-clamp electrophysiology to map insulin and leptin responsive arcuate POMC neurons. Leptin-induced Fos activity within arcuate POMC neurons was localized separate from POMC neurons that express insulin receptor. Moreover, acute responses to leptin and insulin were largely segregated in distinct subpopulations of POMC cells. Collectively, these data suggest that cross talk between leptin and insulin occurs within a network of cells rather than within individual POMC neurons.
Williams
Kevin W
KW
Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Margatho
Lisandra O
LO
Lee
Charlotte E
CE
Choi
Michelle
M
Lee
Syann
S
Scott
Michael M
MM
Elias
Carol F
CF
Elmquist
Joel K
JK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007031:Hypothalamus / Q000166:cytology; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification* / Q000187:drug effects*; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D020738:Leptin; D016761:Oncogene Proteins v-fos; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D011972:Receptor, Insulin