title: Leptin in the hindbrain facilitates phosphorylation of STAT3 in the hypothalamus.
abstract: Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. We recently used low-dose leptin infusions to show that chronic activation of both hypothalamic and hindbrain ObRs is required to reduce body fat. The objective of the present study was to identify the brain nuclei that are selectively activated in rats that received chronic infusion of leptin in both the forebrain and hindbrain. Either saline or leptin was infused into third and fourth ventricles (0.1 μg/24 h in the third ventricle and 0.6 μg/24 h in the fourth ventricle) of male Sprague-Dawley rats for 6 days using Alzet pumps. Rats infused with leptin into both ventricles (LL rats) showed a significant increase in phosphorylated (p)STAT3 immunoreactivity in the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and posterior hypothalamus compared with other groups. No differences in pSTAT3 immunoreactivity were observed in midbrain or hindbrain nuclei despite a sixfold higher infusion of leptin into the fourth ventricle than the third ventricle. ΔFosB immunoreactivity, a marker of chronic neuronal activation, showed that multiple brain nuclei were chronically activated due to the process of infusion, but only the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and ventral tuberomamillary nucleus showed a significant increase in LL rats compared with other groups. These data demonstrate that low-dose leptin in the hindbrain increases pSTAT3 in areas of the hypothalamus known to respond to leptin, supporting the hypothesis that leptin-induced weight loss requires an integrated response from both the hindbrain and forebrain.
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Bhavna N
authors.initials: BN
authors.lastname: Desai
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia ruharris@gru.edu.
authors.forename: Ruth B S
authors.initials: RB
authors.lastname: Harris
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D057967:Infusions, Intraventricular; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D011494:Protein Kinases
keywords: body weight; distributed model; food intake; forebrain; hindbrain; signal transducer and activator of transcription