An in-vitro model of metabolism connecting adipose tissue, endothelial cells and hepatocytes in a multicompartmental bioreactor.

The energy balance in vivo is maintained through inter-organ crosstalk involving several different tissues. As a first step towards recapitulating the metabolic circuitry, hepatocytes, endothelial cells and adipose tissue were connected together in a multicompartmental modular bioreactor (MCmB) to reproduce salient aspects of glucose and lipid metabolism in vitro. We first examined how the 2-way cellular interplay between adipose tissue and endothelial cells affects glucose and lipid metabolism. The hepatocyte cell line HepG2 was then added to the system, creating a 3-way connected culture to determine whether they might normalize circulating metabolite concentrations and correct metabolic shifts that may arise when endothelial cells and adipose tissue are placed in connection. The addition of hepatocytes to the system prevented the drop in glucose, L-alanine and lactate concentrations as well as the rise in free fatty acids. There was no significant glycerol change in either of the connected cultures. The results show that connected cultures recapitulate complex systemic physiological processes such as glucose and lipid metabolism, and that the HepG2 hepatocytes normalize circulating metabolites in this in vitro environment in the presence of other cell types.