Toward a Cell Culture Model of Portal Axis Lipid Handling

Abstract

The health risks posed by excessive visceral white adipose tissue (WAT) may arise from exposure to deleterious intestinal factors in transit through the portal system. These may include an altered bile acid (BA) pool - particularly with respect to 12-hydroxylated BA (12-HBA), which we have previously demonstrated are closely associated with insulin resistance. However, given the complexity of the enterohepatic milieu, we have worked to develop a co-culture system that allows for controlled study of the interactions between human induced pluripotent stem cell (hiPSC) derived adipocytes and primary human intestinal organoids (hIO). We present preliminary data on the characterization of both cellular compartments and their interactions, particularly in the context of BA treatment. We have recapitulated the basic functionality of each tissue type and have found reciprocal, potentially important changes in gene expression in each. However, we also have encountered numerous technical challenges in the development of this co-culture system and provide methodological observations to assist others seeking to work with a co-culture system of this type.