Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus.
Leptin, an adipocyte-derived hormone, reduces food intake by regulating orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived neurotrophic factor is an important anorexigenic factor in the hypothalamus, little is known about the regulation of brain-derived neurotrophic factor expression by leptin in the hypothalamus. In the present study, we examined the effect of leptin on the expression of brain-derived neurotrophic factor in the hypothalamus. I.V. administration of leptin (10 microg/g) led to the increase in the expression of brain-derived neurotrophic factor mRNA, which was observed in the dorsomedial part of the ventromedial hypothalamic nucleus. The increased expression of brain-derived neurotrophic factor mRNA was detected in phosphorylated signal transducer and activator of transcription 3-positive neurons, suggesting that leptin induced brain-derived neurotrophic factor expression in neurons of the dorsomedial part of the ventromedial hypothalamic nucleus. In addition, the expression of brain-derived neurotrophic factor was increased at the protein level in the ventromedial hypothalamic nucleus of leptin-injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers also increased in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus of leptin-injected mice, which were in close apposition to tyrosine kinase receptor B-immunoreactive neurons and colocalized with synaptophysin, a marker of presynaptic terminals. These results suggest that leptin induces brain-derived neurotrophic factor expression in the dorsomedial part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic factor may exert as anorexigenic factors possibly through the activation of tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus.
Komori
T
T
Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
Morikawa
Y
Y
Nanjo
K
K
Senba
E
E
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D012333:RNA, Messenger