Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins.
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.
Yokota
Takafumi
T
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Meka
C S Reddy
CS
Medina
Kay L
KL
Igarashi
Hideya
H
Comp
Phillip C
PC
Takahashi
Masahiko
M
Nishida
Makoto
M
Oritani
Kenji
K
Miyagawa
Jun-Ichiro
J
Funahashi
Tohru
T
Tomiyama
Yoshiaki
Y
Matsuzawa
Yuji
Y
Kincade
Paul W
PW
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
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