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Identification of Macrophage Inhibitory Cytokine-1 in Adipose Tissue and Its Secretion as an Adipokine by Human Adipocytes

Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, United Kingdom

Address all correspondence and requests for reprints to: Dr. Chen Bing, Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, United Kingdom. E-mail: bing{at}liverpool.ac.uk.

Macrophage inhibitory cytokine-1 (MIC-1), a divergent member of the TGF-β 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 H₂O₂ and 15d-prostaglandin J₂. 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.

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