Ate high performance liquid chromatography insulin-like development factor-I interleukin eight c-Jun N-terminal kinase keratinocyte growth aspect mitogen-activated protein kinase malondialdehyde mass RORβ drug spectrometry nuclear factor kappa-light-chain-enhancer of activated B cells nuclear aspect erythroid 2-related element 2 Psoriasis Region and Severity Index principal component analysis protein kinase C Ran-specific GTPase-activating protein 1 reactive oxygen species sodium dodecyl sulfate polyacrylamide gel electrophoresis transforming development factor-1 tumor necrosis element .
Paracrine regulation of fat cell formation in bone marrow cultures by way of adiponectin and prostaglandinsTakafumi Yokota,1 C.S. Reddy Meka,1 Kay L. Medina,1 Hideya Igarashi,1 Phillip C. Comp,2 Masahiko Takahashi,three Makoto Nishida,3 Kenji Oritani,3 Jun-ichiro Miyagawa,three Tohru Funahashi,3 Yoshiaki Tomiyama,3 Yuji Matsuzawa,3 and Paul W. Kincade1Immunobiology 2Departmentand Cancer Program, Oklahoma Medical Study Foundation, Oklahoma City, Oklahoma, USA of Medicine, University of Oklahoma Wellness Sciences Center, Oklahoma City, Oklahoma, USA 3Department of Internal Medicine and Molecular Science, Graduate College of Medicine, Osaka University, Osaka, Japan Address correspondence to: Paul W. Kincade, Immunobiology and Cancer System, Oklahoma Healthcare Investigation Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA. Telephone: (405) 271-7905; Fax: (405) 271-8568; E-mail: [email protected]. Received for publication October 25, 2001, and accepted in revised form April 9, 2002.Adiponectin, an adipocyte-derived hormone, was recently shown to have potential therapeutic applications in diabetes and obesity due to its influence on glucose and lipid metabolism. We located that brown fat in D1 Receptor manufacturer typical human bone marrow consists of this protein and used marrowderived preadipocyte lines and long-term cultures to explore 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 caused 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. Furthermore, adiponectin failed to block fat cell generation when bone marrow cells had 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 for the COX-2 ependent PGs which might be crucial in this approach.J. Clin. Invest. 109:1303310 (2002). doi:10.1172/JCI200214506.Introduction A number of functions attributed to adipose tissue consist of thermoregulation, power storage, estrogen synthesis, and cytokine production. Though fat cells and their precursors happen to be the focus of numerous studies involving obesity, additionally they constitute a normal element of bone marrow. Indeed, adipocytes, hematopoiesis-supporting stromal cells, osteoblasts, and myocytes appear to derive from widespread mesenchymal stem cells in that tissue (1). Cloned preadipocyte lines with all the prospective for differentiation in culture have been incredibly useful for understanding the molecular regulation of differentiation (two). Agents that induce fat cell formation f.