TY - JOUR
T1 - Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity
AU - Zu, Yujiao
AU - Zhao, Ling
AU - Hao, Lei
AU - Mechref, Yehia
AU - Zabet-Moghaddam, Masoud
AU - Keyel, Peter A.
AU - Abbasi, Mehrnaz
AU - Wu, Dayong
AU - Dawson, John A.
AU - Zhang, Ruiwen
AU - Nie, Shufang
AU - Moustaid-Moussa, Naima
AU - Kolonin, Mikhail G.
AU - Daquinag, Alexes C.
AU - Brandi, Luis
AU - Warraich, Irfan
AU - San Francisco, Susan K.
AU - Sun, Xiaocun
AU - Fan, Zhaoyang
AU - Wang, Shu
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5/10
Y1 - 2021/5/10
N2 - 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.
AB - 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.
KW - Adipose stromal cells
KW - Beige adipocytes
KW - Nanoparticles
KW - Obesity
KW - trans-resveratrol
UR - http://www.scopus.com/inward/record.url?scp=85103691405&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2021.03.022
DO - 10.1016/j.jconrel.2021.03.022
M3 - Article
C2 - 33766692
AN - SCOPUS:85103691405
SN - 0168-3659
VL - 333
SP - 339
EP - 351
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -