TY - JOUR
T1 - Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice
AU - Toita, Riki
AU - Kawano, Takahito
AU - Murata, Masaharu
AU - Kang, Jeong Hun
N1 - Funding Information:
The authors thank T. Yamaoka for providing the equipment. This work was supported by a Grant-in-Aid for Challenging Exploratory Research ( 15K12531 ) and for Grant-in-Aid for Young Scientists (B) ( 16K21212 ) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by Fukuoka Foundation for Sound Health Cancer Research Fund.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.biomaterials.2016.09.018
DO - 10.1016/j.biomaterials.2016.09.018
M3 - Article
C2 - 27716475
AN - SCOPUS:84989308879
SN - 0142-9612
VL - 110
SP - 81
EP - 88
JO - Biomaterials
JF - Biomaterials
ER -
