Adipose tissue secretes a variety of adipokines that are directly involved in inflammation and insulin resistance. In this study, we investigated the association of MK with obesity and its actions on adipocytes. Notably, MK levels were increased in adipose tissue of obese mice and in serum of overweight/obese subjects as compared with their controls. In vitro experiments further revealed inhibitory effects of MK on insulin signaling in 3T3-L1 adipocytes, with activation of the STAT3-SOCS3 pathway. Our findings suggest a potential role of MK in obesity-induced insulin resistance. MK is expressed in multiple cell types, including various immune and cancer cells. Here, we found MK expression in both 3T3-L1 preadipocytes and mature adipocytes. In preadipocytes, MK expression increased immediately after differentiation and then declined progressively to the Ibrutinib Src-bcr-Abl inhibitor beginning levels, consistent with its essential role in promoting the mitotic clonal expansion of preadipocytes. In mature adipocytes, MK was regulated by inflammatory modulators. TNF-a treatment led to a marked increase in MK expression. Thus, in line with its inflammatory properties, MK seems closely associated with the inflammatory state of mature adipocytes. In addition to the adipocyte cell line in vitro, MK is also expressed in adipose tissue of mice. Importantly, MK expression was upregulated in epididymal adipose tissue of obese mice. Furthermore, overweight/obese humans had significantly increased serum MK levels compared with control subjects, with a positive correlation between serum MK and BMI. Collectively, MK is associated with obesity in both mice and humans. The mechanisms for MK upregulation in obese adipose tissue may be multiple and remain to be elucidated. TNF-a, which is increased in obesity, induces MK expression in adipocytes, and is therefore a potential candidate for the upregulation of MK. As MK is also expressed by macrophages, which are recruited into adipose tissue in obesity, they may be another source of MK in adipose tissue. In fact, we observed increased expression of MK in stromal cells, which are largely composed of macrophages, in adipose tissue of ob/ob mice compared with controls. Nevertheless, the relative contribution of adipocytes and macrophages to the elevated expression of MK in obese adipose tissue remains to be determined. In addition, as a secreted protein by adipose tissue, MK serum concentration in mice and its relationship with obesity warrant future study. Adipose tissue produces a range of adipokines that are directly involved in insulin resistance. Herein, we showed that MK suppressed insulin signaling in adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 in response to insulin stimulation. These findings provide the first evidence that MK may be a novel inducer of insulin resistance. Since MK expression was increased in adipose tissue of obese mice, it warrants further investigation whether MK induces insulin resistance in vivo.