Obesity represents a heavy burden for modern healthcare. The main challenge facing obesity research progress is the unknown underlying pathways, which limits our understanding of the pathogenesis and developing therapies. Obesity induces specific biochemical environments that impact the different cells and tissues. In this piece of writing, we suggest mimicking obesity-induced in vivo biochemical environments including pH, lipids, hormones, cytokines, and glucose within an in vitro environment. The concept is to reproduce such biochemical environments and use them to treat the tissue cultures, explant cultures, and cell cultures of different biological organs. This will allow us to clarify how the obesity-induced biochemistry impacts such biological entities. It would also be important to try different environments, in terms of the compositions and concentrations of the constitutive elements, in order to establish links between the effects (impaired regeneration, cellular inflammation, etc.) and the factors constituting the environment (hormones, cytokines, etc.) as well as to reveal dose-dependent effects. We believe that such approaches will allow us to elucidate obesity mechanisms, optimize animal models, and develop therapies as well as novel tissue engineering applications.