TY - JOUR
T1 - Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin
AU - Elmquist, Joel K.
N1 - Funding Information:
This work was supported in part by USPHS grants DK53301 and DK56149 and support from Eli Lilly.
PY - 2001/11/12
Y1 - 2001/11/12
N2 - Leptin affects feeding, metabolism, and neuroendocrine status. It is now clearly established that the hypothalamus coordinates these responses, though the specific brain regions engaged by leptin remain unclear. We have used combinations of neuroanatomic techniques to identify candidate pathways in the central nervous system underlying leptin action. 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 sympathetic preganglionic neurons in the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that CART neurons in the RCA and the Arc coexpress pro-opiomelanocortin (POMC) mRNA. Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. Using retrograde tracing with leptin administration, we found retrogradely labeled cells in the Arc contained neuropeptide Y (NPY) mRNA or POMC mRNA. Following leptin administration, NPY cells in the Arc did not express Fos but expressed suppressor of cytokine signaling-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expression in POMC neurons, many of which also innervated the LHA. We suggest that leptin directly activates POMC/CART neurons that project to the LHA, the paraventricular hypothalamic nucleus (PVH), and spinal sympathetic preganglionic neurons. These projections link circulating leptin and neurons that regulate feeding behavior, energy expenditure, and body weight homeostasis.
AB - Leptin affects feeding, metabolism, and neuroendocrine status. It is now clearly established that the hypothalamus coordinates these responses, though the specific brain regions engaged by leptin remain unclear. We have used combinations of neuroanatomic techniques to identify candidate pathways in the central nervous system underlying leptin action. 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 sympathetic preganglionic neurons in the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that CART neurons in the RCA and the Arc coexpress pro-opiomelanocortin (POMC) mRNA. Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. Using retrograde tracing with leptin administration, we found retrogradely labeled cells in the Arc contained neuropeptide Y (NPY) mRNA or POMC mRNA. Following leptin administration, NPY cells in the Arc did not express Fos but expressed suppressor of cytokine signaling-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expression in POMC neurons, many of which also innervated the LHA. We suggest that leptin directly activates POMC/CART neurons that project to the LHA, the paraventricular hypothalamic nucleus (PVH), and spinal sympathetic preganglionic neurons. These projections link circulating leptin and neurons that regulate feeding behavior, energy expenditure, and body weight homeostasis.
KW - AgRP
KW - Arcuate hypothalamic nucleus
KW - CART
KW - Feeding
KW - Melanin-concentrating hormone
KW - Obesity
KW - Orexin
KW - POMC
UR - http://www.scopus.com/inward/record.url?scp=0035851907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035851907&partnerID=8YFLogxK
U2 - 10.1016/S0031-9384(01)00613-8
DO - 10.1016/S0031-9384(01)00613-8
M3 - Article
C2 - 11790432
AN - SCOPUS:0035851907
SN - 0031-9384
VL - 74
SP - 703
EP - 708
JO - Physiology and Behavior
JF - Physiology and Behavior
IS - 4-5
ER -