Melanocortin 4 receptor-mediated hyperphagia and activation of neuropeptide Y expression in the dorsomedial hypothalamus during lactation.
In several hyperphagic models, including lactation, in which hypothalamic melanocortin signaling is reduced, a novel expression of NPY mRNA in the dorsomedial hypothalamus (DMH) has been observed, suggesting that melanocortin signaling and the induced NPY in the DMH may constitute unique neurocircuitry in mediating energy balance. Using lactating rats as a model, the present study first showed that in the DMH abundant alpha-MSH and agouti-related protein fibers are in close apposition to NPY-positive cells. However, no NPY and MC4R (a melanocortin receptor) double-labeled neurons were observed. These data suggested that melanocortin input may synapse on presynaptic terminals that then synapse on DMH NPY cells. To study the function of DMH MC4Rs in energy balance, an MC3/4R-selective agonist, melanotan II (MTII), was injected bilaterally into the DMH. MTII injection significantly suppressed feeding induced by 24 hr fasting or suckling-induced hyperphagia. Furthermore, MTII treatment greatly attenuated suckling-induced NPY expression in the DMH. MTII treatment also stimulated uncoupling protein 1 activity in the brown adipose tissue of suckling female rats, indicative of increased sympathetic outflow. In summary, the present study demonstrated that the melanocortin system in the DMH not only plays an important role in inducing NPY expression in the DMH of lactating rats but also in regulating energy homeostasis, at least in part, by modulating appetite and energy expenditure.
Chen
Peilin
P
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006-3499, USA.
Williams
Sarah M
SM
Grove
Kevin L
KL
Smith
M Susan
MS
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D054369:Agouti-Related Protein; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D006963:Hyperphagia / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D007527:Isoenzymes / Q000235:genetics; D007774:Lactation / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D023421:Models, Animal; D009412:Nerve Fibers / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D007527:Isoenzymes; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D010456:Peptides, Cyclic; D011506:Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C079282:melanotan-II; D000521:alpha-MSH; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1