Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats.
Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB. Therefore, we investigated the BBB in lean and diet-induced obese Lewis rats. To obtain information about the presence of microvessels with barrier dysfunction we examined three brain areas (hypothalamus, cortex, hippocampus) using a monoclonal antibody which detects intact microvessels of the BBB (anti-endothelial barrier antigen, anti-EBA). The results showed a significantly reduced EBA staining in the brain sections of the obese animals, except the hippocampus, compared to the control group. In a second step we injected I125-labeled leptin intravenously (i.v.) in permanent i.v.-cannulated, unrestrained Lewis rats (lean and obese). We measured the radioactivity in the cerebrospinal fluid after puncture of the cisterna magna, in the blood and brain tissue 90 min after injection. The leptin content in the cerebrospinal fluid and brain was not reduced in obese compared to lean rats, thus showing a similar transport capacity of the BBB in both experimental groups. Therefore, the results of the in vivo investigations do not indicate an impairment of the BBB in diet-induced obesity, despite the immunohistological findings. Further functional and morphological studies are necessary to evaluate the specific role of other organs and distinct forms of leptin (free and protein-bound) in the pathogenesis of diet-induced obesity.
Nave
Heike
H
Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany. nave.heike@mh-hannover.de
Kuhlmann
Susanne
S
Brabant
Georg
G
Pabst
Reinhard
R
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D020738:Leptin / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013047:Specific Pathogen-Free Organisms
D000954:Antigens, Surface; D004041:Dietary Fats; D007457:Iodine Radioisotopes; D020738:Leptin; C114781:endothelial barrier antigen, rat