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Body‐on‐a‐chip BOAC: A tool to elucidate clinical observations that involve modulations of the “methylation pathway” in association with the expression of adipokines
Author(s) -
ArizaNieto Magnolia,
Alley Joshua B,
Samy Sanjay A.,
Fitzgerald Laura,
Shuler Michael L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1153.13
Subject(s) - adiponectin , adipokine , dna methylation , epigenetics , epigenome , adipose tissue , leptin , cancer research , progenitor cell , biology , medicine , endocrinology , obesity , stem cell , insulin resistance , microbiology and biotechnology , genetics , gene expression , gene
Obesity is an epidemic in the Unites States that puts individuals at increased risk for cancer, cardiovascular disease and type 2 diabetes mellitus. The link between obesity and cancer may be related to decreased levels of adiponectin, an antiangiogenic, antiatherogenic and antioncogenic biomarker. The anti‐inflammatory and insulin sensitizing properties of adiponectin may be explained by its ability to inhibit endothelial progenitor cells (EPC's) and hematopoietic progenitor cells (HPC's). Our hypothesis is that by nutritionally limiting the levels of homocysteine, epigenetic alternations in the levels of NPY will lead to increased levels of adiponectin. The goal of this research is to observe the changes in circulating levels of adiponectin, homocysteine and NPY in vivo and an attempt is being made to replicate the observations in vitro using the well defined “body‐on‐a‐chip” BOAC systems. Liver, omental fat and mononuclear cells are used to genotype and phenotype each donor. Genetically characterized bone marrow and/or adipose derived mesenchymal stem cells are isolated, expanded and differentiated. The BOAC is a microfabricated device based on a physiologically based‐pharmacokinetic (PBPK) model and combined with cell cultures is being used to study changes in the epigenome. The genotyped BOAC is a new tool to study variability in nutrient bioavailability, modulations of the methylation pathway, and adipokine expression and signaling. Funding Cornell Center on the Microenvironment and Metastasis (CMM) outreach pilot grant and Guthrie Foundation Investigator‐Initiated Research Grant.