Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis.
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/loxP 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.
Balthasar
Nina
N
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue RN, Boston, MA 02215, USA.
Coppari
Roberto
R
McMinn
Julie
J
Liu
Shun M
SM
Lee
Charlotte E
CE
Tang
Vinsee
V
Kenny
Christopher D
CD
McGovern
Robert A
RA
Chua
Streamson C
SC
Elmquist
Joel K
JK
Lowell
Bradford B
BB
D000367:Age Factors; D000818:Animals; D001823:Body Composition / Q000235:genetics; D001835:Body Weight / Q000502:physiology*; D004435:Eating / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D049452:Green Fluorescent Proteins; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D054411:Receptors, Leptin; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism
D020738:Leptin; D008164:Luminescent Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C515447:leptin receptor, mouse; D049452:Green Fluorescent Proteins; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin