Engineering an energy-dissipating hybrid tissue in vivo for obesity treatment

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host’s energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight. [Display omitted] •Human A549 cells expressing UCP1 perform uncoupled respiration•KSP in the alginate-gelatin induces immunosuppression and ECM production•A549-UCP1 cells and the matrix form an energy-dissipating hybrid tissue•EDHT reduces fat and relieves obesity-associated pathological conditions Wang et al. show the construction of an energy-dissipating hybrid tissue (EDHT) in vivo. EDHT demonstrates high efficacy in managing body weight and safety in mice, representing another strategy for potential anti-obesity therapy.