Translation of academic research into clinical practice is dependent on tools and strategies that allow the understanding of an extremely complex system. The liver has a unique role in the regulation and maintenance of mammalian metabolism(Finkelstein, 1998) and as a consequence a balanced state of the epigenome. Our group aims to facilitate the understanding of the modulations of the S-Adenosylmethionine metabolic pathway (SAM) in humans that in turn regulate modulations of the epigenome. Extensive published research reveals, a common etiology in metabolic disorders is a dysregulatory state of insulin secretion, adipokine signaling and a subsequent dysregulatory state of the epigenome. 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 metabolic surgery for weight loss; all donors (n=43, and 42 controls) signed informed consent. This dual model includes 1) a clinical precision medicine model and 2) liver in vitro model, based on hepatogenesis of mesenchymal stem cells (MSCs) (Stock et al., 2010) isolated from the same donors were used to profile the episensor. Multiple in vitro cell model platforms are being tested (Esch et al., 2011).Expression profiles of a combination of proprietary transcripts followed the MIQE guidelines (referred here as episensors). Plasma metabolites and the episensors were assessed in human plasma, in the case of the in vitro model surrogate blood was used. The patients (n=43) that had metabolic surgery lost an average of 47±12 % excess BMI after 12 weeks. All patients in this cohort resolved type 2 diabetes, however not all of them resolved insulin insensitivity, adipokine, and epigenetic dysregulatory states. Our data suggest the dysregulatory state can be assessed with the episensors, Furthermore, physical activity is a major contributor to the modulations of the SAM’s pathway. This research suggests the episensors are an extraordinary tool for monitoring changes in the SAM’s pathway in vivo and/or in vitro, to investigate the etiology, prevention or treatment of metabolic disorders associated with dysregulatory states of the epigenome.