期刊
JOURNAL OF CONTROLLED RELEASE
卷 333, 期 -, 页码 339-351出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.03.022
关键词
Obesity; Adipose stromal cells; trans-resveratrol; Beige adipocytes; Nanoparticles
资金
- National Center for Complementary and Integrative Health [1R15AT008733, 1R15AT010395]
- American Heart Association [19AIREA34480011, 16SDG30200001]
- Harry E. Bovay, Jr. Foundation
- TTU Obesity Research Cluster
- U.S. Department of Agriculture, Agriculture Research Service [58-1950-4-003]
Research shows targeted nanoparticle delivery of browning agents could induce differentiation of adipose stromal cells into beige adipocytes, leading to decreased fat mass, improved glucose metabolism, and reduced inflammation, providing a transformative technology in combating obesity and its comorbidities.
Enhancing thermogenic energy expenditure via promoting the browning of white adipose tissue (WAT) is a potential therapeutic strategy to manage energy imbalance and the consequent comorbidities associated with excess body weight. Adverse effects and toxicities of currently available methods to induce browning of WAT have retarded exploration of this promising therapeutic approach. Targeted delivery of browning agents to adipose stromal cells (ASCs) in subcutaneous WAT to induce differentiation into beige adipocytes may overcome these barriers. Herein, we report for the first time, ASC-targeted delivery of trans-resveratrol (R), a representative agent, using ligand-coated R-encapsulated nanoparticles (L-Rnano) that selectively bind to glycanation sitedeficient decorin receptors on ASCs. After biweekly intravenous administration of L-Rnano to obese C57BL/6 J mice for 5 weeks targeted R delivery significantly induced ASCs differentiation into beige adipocytes, which subsequently resulted in 40% decrease in fat mass, accompanied by improved glucose homeostasis and decreased inflammation. Our results suggest that the ASC-targeted nanoparticle delivery of browning agents could be a transformative technology in combating obesity and its comorbidities with high efficacy and low toxicity.
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