title: Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins.
abstract: Adiponectin, an adipocyte-derived hormone, was recently shown to have potential therapeutic applications in diabetes and obesity because of its influence on glucose and lipid metabolism. We found that brown fat in normal human bone marrow contains this protein and used marrow-derived preadipocyte lines and long-term cultures to explore potential roles in hematopoiesis. Recombinant adiponectin blocked fat cell formation in long-term bone marrow cultures and inhibited the differentiation of cloned stromal preadipocytes. Adiponectin also caused elevated expression of cyclooxygenase-2 (COX-2) by these stromal cells and induced release of prostaglandin E(2) (PGE(2)). The COX-2 inhibitor Dup-697 prevented the inhibitory action of adiponectin on preadipocyte differentiation, suggesting involvement of stromal cell-derived prostanoids. Furthermore, adiponectin failed to block fat cell generation when bone marrow cells were derived from B6,129S(Ptgs2tm1Jed) (COX-2(+/-)) mice. These observations show that preadipocytes represent direct targets for adiponectin action, establishing a paracrine negative feedback loop for fat regulation. They also link adiponectin to the COX-2-dependent PGs that are critical in this process.
authors.affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.forename: C S Reddy
authors.initials: CS
authors.lastname: Meka
authors.forename: Kay L
authors.initials: KL
authors.lastname: Medina
authors.forename: Hideya
authors.initials: H
authors.lastname: Igarashi
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Comp
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Miyagawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kincade
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D052242:Adiponectin; D002001:Adipose Tissue, Brown / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D019899:Paracrine Communication / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D011506:Proteins; D011994:Recombinant Proteins; D013876:Thiophenes; C064874:DuP 697; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone