Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice.

Obesity is associated with chronic inflammation and is known as a major risk factor for several diseases including chronic kidney disease, diabetes, and cardiovascular diseases. Macrophages play a critical role in the development of obesity-induced inflammation. Efficient delivery of therapeutic anti-inflammatory molecules, such as interleukin (IL)-10, to macrophages can dramatically improve therapeutic efficacy of obesity treatments. We used liposomes containing the 'eat-me' signal phosphatidylserine (PS) (PS-containing liposomes; PSL), which have macrophage targeting ability and anti-inflammatory functions, as a biomaterial carrier for the delivery of IL-10 to macrophages. The IL-10-conjugated PSL (PSL-IL10) showed high affinity for macrophages. In obese mice, PSL-IL10 treatment exhibited significant anti-obesity and anti-inflammatory effects, such as reduced serum total cholesterol, adipocyte size, crown-like structures, proinflammatory cytokine secretion (IL-6 and tumor necrosis factor α) in adipose tissue, liver injury, hepatic steatosis, and inflammation foci, while treatment with IL-10 or PSL alone did not. These findings suggest that the PSL-IL10 has macrophage targeting ability and enhanced anti-inflammatory effect due to the synergistic anti-inflammatory effects of IL-10 and PSL, and can be used as a macrophage-targeted therapeutic material for inflammation-related diseases, including obesity.