Ate high overall performance liquid chromatography insulin-like growth factor-I interleukin eight c-Jun N-terminal kinase keratinocyte development element mitogen-activated protein kinase malondialdehyde mass spectrometry nuclear element kappa-light-chain-enhancer of activated B cells nuclear element erythroid 2-related aspect 2 Psoriasis Region and Severity Index principal element evaluation protein kinase C Ran-specific GTPase-activating protein 1 reactive oxygen species sodium dodecyl sulfate polyacrylamide gel electrophoresis transforming growth factor-1 tumor necrosis element .
Paracrine regulation of fat cell formation in bone marrow cultures through adiponectin and prostaglandinsTakafumi Yokota,1 C.S. Reddy Meka,1 Kay L. Medina,1 Hideya Igarashi,1 Phillip C. Comp,two Masahiko Takahashi,3 Makoto Nishida,three Kenji Oritani,three Jun-ichiro Miyagawa,3 Tohru Funahashi,three Yoshiaki Tomiyama,three Yuji Matsuzawa,three and Paul W. Kincade1Immunobiology 2Departmentand Cancer System, Sigma 1 Receptor site Oklahoma Health-related Analysis Foundation, Oklahoma City, Oklahoma, USA of Medicine, University of Oklahoma Overall health Sciences Center, Oklahoma City, Oklahoma, USA 3Department of 5-HT4 Receptor Species Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan Address correspondence to: Paul W. Kincade, Immunobiology and Cancer System, Oklahoma Health-related Study Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA. Phone: (405) 271-7905; Fax: (405) 271-8568; E-mail: [email protected]. Received for publication October 25, 2001, and accepted in revised kind April 9, 2002.Adiponectin, an adipocyte-derived hormone, was recently shown to have possible therapeutic applications in diabetes and obesity because of its influence on glucose and lipid metabolism. We identified that brown fat in regular human bone marrow consists of this protein and made use of marrowderived preadipocyte lines and long-term cultures to discover possible 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 brought on elevated expression of cyclooxygenase-2 (COX-2) by these stromal cells and induced release of prostaglandin E2 (PGE2). The COX-2 inhibitor Dup-697 prevented the inhibitory action of adiponectin on preadipocyte differentiation, suggesting involvement of stromal cell erived prostanoids. Additionally, adiponectin failed to block fat cell generation when bone marrow cells have been derived from B6,129SPtgs2tm1Jed (COX-2+/ mice. These observations show that preadipocytes represent direct targets for adiponectin action, establishing a paracrine unfavorable feedback loop for fat regulation. In addition they link adiponectin to the COX-2 ependent PGs that are vital in this approach.J. Clin. Invest. 109:1303310 (2002). doi:10.1172/JCI200214506.Introduction Numerous functions attributed to adipose tissue contain thermoregulation, power storage, estrogen synthesis, and cytokine production. Although fat cells and their precursors have been the focus of quite a few studies involving obesity, additionally they constitute a regular component of bone marrow. Certainly, adipocytes, hematopoiesis-supporting stromal cells, osteoblasts, and myocytes seem to derive from popular mesenchymal stem cells in that tissue (1). Cloned preadipocyte lines together with the potential for differentiation in culture have already been really precious for understanding the molecular regulation of differentiation (2). Agents that induce fat cell formation f.
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