Adipose stem cell-targeted local delivery of forskolin induces de novo beige adipogenesis and adipose tissue browning to combat obesity.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Inducing white adipose tissue (WAT) browning is a promising strategy to combat obesity and metabolic disorders. However, current browning inducers often suffer from off-target effects and poor durability. Beige adipocytes, which can arise through de novo differentiation from adipose-derived stromal/stem cells (ASCs), offer a potential avenue for sustained thermogenesis. Here, we identified that forskolin (FSK) effectively induced the differentiation of C3H10T1/2 cells (a mesenchymal stem cell line) into beige adipocytes, evidenced by multilocular lipid droplets, enhanced mitochondrial biogenesis and function, and elevated uncoupling protein 1 expression. To overcome its poor bioavailability and lack of targeting specificity, we developed ASCs-targeting-peptide (ASP, sequence: GSWKYWFGEGGC) modified FSK nanoparticles (ASP@FSK NPs) by encapsulating FSK in the hybrid FDA-approved biodegradable polymers poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG)-ylated PLGA. ASP@FSK NPs selectively bind to glycanation site-deficient decorin (ΔDCN) receptors on ASCs, enabling prolonged retention and localized delivery within inguinal WAT (iWAT). In a high-fat diet-induced obesity model, local administration of ASP@FSK NPs significantly reduced body weight (∼30%), promoted de novo browning of iWAT, and alleviated liver steatosis in high-fat diet-induced obese mice, while expa

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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