Farnesol-Loaded Nanoliposomes Inhibit Inflammatory Gene Expression in Primary Human Skeletal Myoblasts

Simple Summary Obesity leads to the accumulation of free fatty acids (FFAs) and inflammation in skeletal muscle, which results in the loss of muscle mass and function. Farnesol is a natural hydrophobic compound from plants with poor bioavailability. We used a liposomal delivery system to direct farnesol into muscle cells and examined its possible beneficial effects on restraining inflammation. Our data strongly suggest that farnesol acts as a potent inhibitor of inflammatory gene expression in human myoblasts. There is a substantial unmet need for the treatment of skeletal muscle mass loss that is associated with aging and obesity-related increases in FFA. Unsaturated FFAs stimulate the inflammatory gene expression in human skeletal myoblasts (SkMs). Farnesol is a hydrophobic acyclic sesquiterpene alcohol with potential anti-inflammatory effects. Here, we created farnesol-loaded small unilamellar (SUVs) or multilamellar lipid-based vesicles (MLVs), and investigated their effects on inflammatory gene expression in primary human skeletal myoblasts. The attachment of SUVs or MLVs to SkMs was tracked using BODIPY, a fluorescent lipid dye. The data showed that farnesol-loaded SUVs reduced FFA-induced IL6 and LIF expression by 77% and 70% in SkMs, respectively. Farnesol-loaded MLVs were less potent in inhibiting FFA-induced IL6 and LIF expression. In all experiments, equal concentrations of free farnesol did not exert significant effects on SkMs. This report suggests that farnesol, if efficiently directed into myoblasts through liposomes, may curb FFA-induced inflammation in human skeletal muscle.