Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes.
Leptin, an adipokine mainly produced by adipocytes, has been well characterized with regard to its regulatory function on immune cells. Thus the question occurred of how adipocytes and preadipocytes interact with the immune system and whether or not this communication is regulated by leptin. With the present study we evaluated the Toll-like receptor (TLR) expression and TLR ligand-specific activation of murine preadipocytes and adipocytes in the presence [wild type (WT), 3T3L1] or absence of leptin (ob/ob) or leptin signaling (db/db). The ob/ob as well as db/db adipocytes and preadipocytes were characterized by a significant up-regulation of TLR1 to -9 expression when compared with WT cells. In WT preadipocytes the TLR responsiveness increased during maturation to adipocytes; however, stimulation of ob/ob and db/db cells resulted in a 10- to 20-fold higher interleukin-6 production. Signaling studies revealed, in addition to the increased TLR expression, alterations in the phosphoinositide 3 kinase signaling cascade in ob/ob and db/db cells as an explanation for this increased responsiveness. In conclusion, the present study indicates the expression and responsiveness of TLR1 to -9 in murine preadipocytes as well as adipocytes, both of which are strongly regulated by the adipokine leptin. In summary, these data further emphasize the role of fat tissue in the immune system.
Batra
Arvind
A
Department of Medicine I, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Pietsch
Jeannette
J
Fedke
Inka
I
Glauben
Rainer
R
Okur
Besir
B
Stroh
Thorsten
T
Zeitz
Martin
M
Siegmund
Britta
B
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000730:Androstadienes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054411:Receptors, Leptin; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt; D054411:Receptors, Leptin; D051193:Toll-Like Receptors; D000077191:Wortmannin; C515447:leptin receptor, mouse