期刊
BIOMATERIALS SCIENCE
卷 11, 期 16, 页码 5663-5673出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d3bm00619k
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This study proposes a local administration strategy for obesity treatment using R-Ha(Chr) fiber rods loaded with chrysin and F-Ats(Rk) fiber fragments loaded with raspberry ketone. This strategy improves lipid metabolism, reduces inflammation, and leads to weight loss.
Obesity has become a worldwide public health problem and continues to be one of the leading causes of chronic diseases. Obesity treatment is challenged by large drug doses, high administration frequencies and severe side effects. Herein, we propose an antiobesity strategy through the local administration of R-Ha(Chr) fiber rods loaded with chrysin and grafted with hyaluronic acid and F-Ats(Rk) fiber fragments loaded with raspberry ketone and grafted with adipocyte target sequences (ATSs). The hyaluronic acid grafts double the uptake levels of R-Ha(Chr) by M1 macrophages to promote phenotype transformation from M1 to M2 through upregulating CD206 and downregulating CD86 expressions. ATS-mediated targeting and sustained release of raspberry ketone from F-Ats(Rk) increase the secretion of glycerol and adiponectin, and Oil red O staining shows much fewer lipid droplets in adipocytes. The combination treatment with F-Ats(Rk) and the conditioned media from R-Ha(Chr)-treated macrophages elevates adiponectin levels, suggesting that M2 macrophages may secrete anti-inflammatory factors to stimulate adipocytes to produce adiponectin. Diet-induced obese mice showed significant weight losses of inguinal (49.7%) and epididymal (32.5%) adipose tissues after R-Ha(Chr)/F-Ats(Rk) treatment, but no effect was observed on food intake. R-Ha(Chr)/F-Ats(Rk) treatment reduces adipocyte volumes, lowers serum levels of triglycerides and total cholesterol and restores adiponectin levels to those of normal mice. In the meantime, R-Ha(Chr)/F-Ats(Rk) treatment significantly elevates the gene expression of adiponectin and interleukin-10 and downregulates tissue necrosis factor-& alpha; expression in the inguinal adipose tissues. Thus, local injection of cell-targeting fiber rods and fragments demonstrates a feasible and effective antiobesity strategy through improving lipid metabolism and normalizing the inflammatory microenvironment.
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