Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes.
Macrophage inhibitory cytokine-1 (MIC-1), a divergent member of the TGF-beta superfamily, is involved in the control of multiple cellular processes and mediates cachexia through the inhibition of appetite. Adipose tissue as an endocrine organ secretes proteins (adipokines) that regulate energy homeostasis and other cellular functions. This study investigated whether MIC-1 is expressed in adipose tissue and whether MIC-1 is a secretory product of adipocytes. Mouse and human adipose tissues were collected from different depots. 3T3-L1 preadipocytes and human preadipocytes were induced to differentiate into adipocytes in cell culture. MIC-1 mRNA was detected in the major mouse adipose depots (epididymal, perirenal, sc). In these depots, MIC-1 gene expression was evident in both isolated mature adipocytes and stromal-vascular cells. In 3T3-L1 adipocytes, MIC-1 mRNA was detected before and after differentiation. MIC-1 mRNA and protein secretion were evident in human preadipocytes as well as differentiated adipocytes. MIC-1 production by human adipocytes was stimulated by H(2)O(2) and 15d-prostaglandin J(2). In addition, recombinant MIC-1 increased adiponectin secretion by differentiated human adipocytes. MIC-1 mRNA and protein were also observed in human sc and visceral fat. MIC-1 mRNA levels were positively correlated with adiponectin mRNA. Moreover, MIC-1 mRNA was negatively associated with body mass index and body fat mass in human subjects. We conclude that MIC-1 is expressed in adipose tissue and secreted from adipocytes and is therefore a new adipokine. MIC-1 may have a paracrine role in the modulation of adipose tissue function and body fat mass.
Ding
Qi
Q
Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
Mracek
Tomas
T
Gonzalez-Muniesa
Pedro
P
Kos
Katarina
K
Wilding
John
J
Trayhurn
Paul
P
Bing
Chen
C
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D055436:Growth Differentiation Factor 15 / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
C477819:15-deoxyprostaglandin J2; D054392:Adipokines; D055436:Growth Differentiation Factor 15; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D015230:Prostaglandin D2