Downregulated expression of the secreted glycoprotein follistatin-like 1 (Fstl1) is a robust hallmark of preadipocyte to adipocyte conversion

摘要: Obesity is a public health crisis in the United States. Targeting preadipocyte to adipocyte conversion may be an effective approach regulate adipose mass. Using differential screening we identified Fstl1, secreted glycoprotein with roles immunomodulation, cell growth, cardioprotection, and vascularization, as "preadipokine". Fstl1 highly expressed 3T3-L1 preadipocytes dramatically downregulated early their differentiation adipocytes. Northern blot analysis of murine tissues reveals white tissue (WAT), lung heart primary sites transcript expression. In WAT, restricted preadipocyte-containing stromal-vascular population. Time course studies multiple adipogenesis models reveal downregulation hallmark brown conversion. By Western blot, show culture media contains high levels protein that rapidly decline Moreover, observe correlation between phenotype expression TNFalpha-mediated de-differentiation adipocytes accompanied by re-expression protein. Treatment panel 18 hormones other agents revealed demethylating agent 5-aza-cytidine decreases approximately 90%. Furthermore, 10 additional preadipocyte-expressed genes analyzed find Pref-1, Col1A1, Sca-1/Ly6a, Lox Thbs2, are also 5-aza-cytidine. luciferase reporter constructs containing 791 or 3922 bp 5' flanking region, determine negative transcriptional regulation Kruppel-like factor 15. Together, our data suggest important feature