title: Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells.
abstract: Adiponectin has recently been reported to generate a negative energy balance by increasing energy expenditure. However, it is unclear whether such effects require the presence and direct action of the adiponectin protein in the central nervous system. In this study, neither radiolabeled nonglycosylated nor glycosylated globular adiponectin crossed the blood-brain barrier (BBB) in mice. In addition, adiponectin was not detectable in human cerebrospinal fluid using various established methods. Using murine cerebral microvessels, we demonstrated expression of adiponectin receptors, which are upregulated during fasting, in brain endothelium. Interestingly, treatment with adiponectin reduced secretion of the centrally active interleukin-6 from brain endothelial cells, a phenomenon that was paralleled by a similar trend of other proinflammatory cytokines. In summary, our data suggest that direct effects of endogenous adiponectin on central nervous system pathways are unlikely to exist. However, the identification of adiponectin receptors on brain endothelial cells and the finding of a modified secretion pattern of centrally active substances from BBB cells provides an alternate explanation as to how adiponectin may evoke effects on energy metabolism.
authors.affiliation: Dept. of Clinical Nutrition, German Institute of Human Nutrition Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. spranger@mail.dife.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Sulekha
authors.initials: S
authors.lastname: Verma
authors.forename: Isabel
authors.initials: I
authors.lastname: Göhring
authors.forename: Thomas
authors.initials: T
authors.lastname: Bobbert
authors.forename: Joseph
authors.initials: J
authors.lastname: Seifert
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Hileman
authors.forename: Matthias
authors.initials: M
authors.lastname: Tschöp
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D052242:Adiponectin / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism; D044967:Serum / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D016207:Cytokines; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface