Fetal bovine serum (FBS) is an essential culture supplement for adipocyte differentiation of various adipogenic precursor cells. Adipocyte differentiation greatly varies depending on the type of serum in the differentiation medium. In this study, we found that FBS supported adipocyte differentiation of 3T3-L1 cells to a significantly higher extent than other types of bovine serum such as adult bovine serum (ABS). This differential adipogenic effect of bovine serum was shown to be due to the protein contents of bovine sera, indicating the presence of an adipogenic protein(s) in FBS. Serum proteome analysis identified tetranectin as an adipogenic protein. The adipogenic effect of tetranectin was confirmed by supplementation of FBS-containing differentiation medium with anti-tetranectin antibody, which suppressed adipocyte differentiation of 3T3-L1 cells. These results demonstrate that tetranectin is an adipogenic serum protein mediating the adipogenic effect of FBS. (C) 2015 Elsevier Inc. All rights reserved.