Our group is working on the development of a human in vitro model to study epigenetic dysregulations in a personalized manner. Our goal is to identify secretory biosensors of the epigenome that could be used both in vivo and in vitro. Human in vitro models loaded with differentiated mesenchymal stem cells depend on reliable biosensors to study changes in the human epigenome (Shuler, 2012). We hypothesize that the liver is a major target organ of adiponectin the most abundant peptide hormone expressed in adipose tissue. And as a consequence the differential expression of liver target genes that regulate glucose and insulin homeostasis as well as fatty acid oxidation appear to be controlled by the adipose-liver signaling interactions. DNMT1 is a key regulator of normal liver function (Raggi, et al. , 2014). CD14 is a peptide antigen associated with microvesicles/exosomes (Kranendonk, et al. , 2014), which are important transportation vehicles for proteins and microRNAs in the human body. This in vivo and in vitro study is compliant with ethics review, as an IRB approved clinical trial (GHS # 1207-27). Subjects enrolled were patients scheduled to undergo gastric bypass surgery for weight loss; all donors (n=47) signed informed consent. Expression profiles of liver DNMT1, CD14 and GAPDH followed the MIQE guidelines. Fasting plasma was used for the assessment of plasma total adiponectin and CD14, as well as for the isolation of mature microRNAs. Differentiated mesenchymal stem cells (MSCs) isolated from the same donors are being used in an attempt to study cell signaling interactions in vitro (Stock, et al. , 2010). Spearman’s correlation analysis reveal an inverse significant association between liver DNMT1 and liver CD14 (r=-0.5501, p=0.0180, n=18) as well as with plasma adiponectin (r = -0.7614, p = 0.0002, n = 18). To the best of our knowledge, this is the first report of the association between total plasma adiponectin and liver DNMT1 in humans. Three microRNA’s (hsa-miR148, hsa-miR-210, and hsa-miR22) have been identified for their potential regulatory loops with liver DNMT1 and their profiles are under evaluation. In summary fasting plasma total adiponectin, circulating CD14, mature microRNAs as well as liver expression profiles of DNMT1 and CD14 affect a multitude of regulatory signaling pathways that could potentially aid in the elucidation on the onset of obesity and the role of the adipose-liver signaling interactions.