Physiological processes involve a complex network of signaling molecules that act through paracrinal or endocrinal pathways; however, traditional in vitro models cannot mimic these interactions because of the lack of a dynamic cross-talk between cells belonging to different tissues. The multicompartmental modular bioreactor is a novel cell culture system where hepatocytes and adipose tissue are shown to interact in a more physiological manner. In the multicompartmental modular bioreactor, cells and tissues can be cultured in a common medium, which flows through the system acting as the bloodstream. Primary rat hepatocytes and adipose tissue were cultured separately and together in conventional conditions and in the bioreactor. Urea synthesis, albumin secretion, glycerol, free fatty acid, and glucose concentrations were analyzed and compared. The dynamic connected culture of adipose tissue and hepatocytes led to a significant enhancement of hepatic function in terms of increase of albumin and urea production with respect to conventional cultures. Interestingly, the glycerol gradually released from adipose tissue was buffered in the dynamic connected culture, manifesting a homeostatic-like control. These data show that the dynamic culture not only improves hepatocyte function, but also allows a cross-talk between tissues, leading to enhanced metabolic regulation in vitro.