title: An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor.
abstract: The energy balance in vivo is maintained through inter-organ cross-talk involving several different tissues. As a first step towards recapitulating the metabolic circuitry, hepatocytes, endothelial cells and adipose tissue were connected in a multicompartmental modular bioreactor to reproduce salient aspects of glucose and lipid metabolism in vitro. We first examined how the two-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 three-way connected culture, to determine whether circulating metabolite concentrations were normalized, or whether metabolic shifts, which may arise when endothelial cells and adipose tissue are placed in connection, were corrected. The addition of hepatocytes to the system prevented the drop in the concentrations of glucose, L-alanine and lactate, and the rise in that of free fatty acids. There was no significant change in glycerol levels in either of the connected cultures. The results show that connected cultures recapitulate complex physiological systemic 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.
authors.affiliation: Centro Interdipartimentale di Ricerca "E. Piaggio", Faculty of Engineering, University of Pisa, Pisa, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Vinci
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.forename: Francesco
authors.initials: F
authors.lastname: Meduri
authors.forename: Silvia
authors.initials: S
authors.lastname: Fattori
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marescotti
authors.forename: Maura
authors.initials: M
authors.lastname: Castagna
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Arti
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism
chemical_list: D000418:Albumins; D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D005947:Glucose; D000409:Alanine; D005990:Glycerol