title: Blockade of the cerebral aqueduct in rats provides evidence of antagonistic leptin responses in the forebrain and hindbrain.
abstract: Previously, we reported that low-dose leptin infusions into the fourth ventricle produced a small but significant increase in body fat. These data contrast with reports that injections of higher doses of leptin into the fourth ventricle inhibit food intake and weight gain. In this study, we tested whether exogenous leptin in the fourth ventricle opposed or contributed to weight loss caused by third ventricle leptin infusion by blocking diffusion of CSF from the third to the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions of PBS or 0.3 μg leptin/24 h from miniosmotic pumps. After 4 days, rats received a 3-μl cerebral aqueduct injection of saline or of thermogelling nanoparticles (hydrogel) that solidified at body temperature. Third ventricle leptin infusion inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated the effect of leptin on food intake and weight loss but had no effect on the weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but did not change energy expenditure. Blocking the aqueduct decreased expenditure of rats infused with PBS or leptin. Infusion of leptin into the third ventricle increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3 but decreased p-STAT3 in the medial NTS. These results support previous observations that low-level activation of hindbrain leptin receptors has the potential to blunt the catabolic effects of leptin in the third ventricle.
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Vaill
authors.forename: Bhavna N
authors.initials: BN
authors.lastname: Desai
authors.forename: Ruth B S
authors.initials: RB
authors.lastname: Harris
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D002535:Cerebral Aqueduct / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D020546:Fourth Ventricle / Q000187:drug effects / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D020542:Third Ventricle / Q000187:drug effects / Q000378:metabolism
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: body composition; calorimetry; food intake; signal transducer and activator of transcription 3