Leptin activates hypothalamic CART neurons projecting to the spinal cord.
The adipocyte-derived hormone leptin decreases body weight in part by activating the sympathetic nervous system, resulting in increased thermogenesis and energy expenditure. We investigated hypothalamic pathways underlying leptin's effects on stimulating the sympathetic nervous system. We found that leptin activates neurons in the retrochiasmatic area (RCA) and lateral arcuate nucleus (Arc) that innervate the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that most CART-containing neurons in the RCA and Arc of the hypothalamus also contain proopiomelanocortin (POMC) mRNA. The finding that leptin activates CART/POMC neurons innervating sympathetic preganglionic neurons in the thoracic spinal cord suggests that this pathway may contribute to the increased thermogenesis and energy expenditure and decreased body weight observed following leptin administration.
Elias
C F
CF
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lee
C
C
Kelly
J
J
Aschkenasi
C
C
Ahima
R S
RS
Couceyro
P R
PR
Kuhar
M J
MJ
Saper
C B
CB
Elmquist
J K
JK
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D020738:Leptin; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009928:Organ Specificity; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D020738:Leptin; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin