Injectable multifunctional hydrogels for adipose tissue remodeling to treat obesity and alleviate metabolic syndrome.

Dysfunction of adipose tissue in obese individuals is associated with metabolic imbalances. Current treatments focus on reducing calorie intake and increasing exercise but have unsatisfactory efficacy and significant side effects. Here, a subcutaneously in situ formed therapeutic hydrogel (RL lip@gel) that can simultaneously modulate the inflammatory environment of adipose tissue and induce adipocyte browning is developed to combat obesity. The alginate solution encapsulates the anti-inflammatory natural flavonoid luteolin and rosiglitazone-loaded liposomes (RL lip), which can be formed as an in situ hydrogel through crosslinking with divalent metal ions in adipose tissue following subcutaneous injection. RL lip@gel not only reprograms M1-like adipose tissue macrophages into an M2-like phenotype but diminishes the expression of proinflammatory cytokine, thereby decreasing systemic glucose resistance and lipid storage. Meanwhile, rosiglitazone embedded within the adipose tissue promotes the browning of white adipocytes, and boosts energy expenditure, with further enhancement from luteolin, as demonstrated by decreased white adipose tissue masses. This localized intervention not only ensures the efficacy of combating obesity systemically but enhances overall metabolism while minimizing side effects.