Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity

Yujiao Zu, Ling Zhao, Lei Hao, Yehia Mechref, Masoud Zabet-Moghaddam, Peter A. Keyel, Mehrnaz Abbasi, Dayong Wu, John A. Dawson, Ruiwen Zhang, Shufang Nie, Naima Moustaid-Moussa, Mikhail G. Kolonin, Alexes C. Daquinag, Luis Brandi, Irfan Warraich, Susan K. San Francisco, Xiaocun Sun, Zhaoyang Fan, Shu Wang

Research output: Contribution to journalArticlepeer-review

Abstract

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 site-deficient 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.

Original languageEnglish
Pages (from-to)339-351
Number of pages13
JournalJournal of Controlled Release
Volume333
DOIs
StatePublished - May 10 2021

Keywords

  • Adipose stromal cells
  • Beige adipocytes
  • Nanoparticles
  • Obesity
  • trans-resveratrol

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