title: Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice.
abstract: 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.
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan; Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. Electronic address: toita-r@aist.go.jp.
authors.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka, 565-8565, Japan. Electronic address: jrjhkang@ncvc.go.jp.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D004357:Drug Synergism; D005234:Fatty Liver / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000494:pharmacology; D008081:Liposomes; D008099:Liver / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy*; D010718:Phosphatidylserines / Q000737:chemistry; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D008081:Liposomes; D010718:Phosphatidylserines; D016753:Interleukin-10
keywords: Cytokine; Inflammatory diseases; Liposome; Macrophage; Obesity