Peptide-based high-density lipoprotein promotes adipose tissue browning and restrains development of atherosclerosis and type 2 diabetes

Ruodan Xu, Shizhong Li, Mingfei Shi, Ziyun Li, Yin Wang, Jing Li, Qiang Li, Lasse Hyldgaard Klausen, An Li, Haiyu Zhao, Menglin Chen, Jingqing Hu*, MD Dong*, Ning Li*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Atherosclerosis (AS) and type 2 diabetes (T2DM) are metabolically associated disorders characterized by dyslipidemia or hyperglycemia. Apolipoprotein (Apo)A-I or ApoA-I-derived reconstituted high-density lipoprotein (rHDL)-raising therapies have been proposed beneficial in both pathologies. Currently, high-cost of ApoA-I and complexity in producing rHDL have set financial and manufacturing barriers to HDL-focused therapies. Here, we construct a peptide-based HDL (pHDL) by microfluidics, simply employing dimeric form of ApoA-I mimetic peptide 4F and phospholipids. Morphologically, pHDL adopts nano-discoidal model of HDL. More intriguingly in function, pHDL predominantly triggers activation of adipose tissue browning in both AS and T2DM experimental models, contributing to a potent management of dyslipidemia and hyperglycemia. Activation of fat browning and benefits in both AS and T2DM provide new insights into pHDL as a potential therapeutic candidate to complement current pharmacological arsenals for metabolic defects, and engineering of pHDL will further facilitate clinical translation of synthetic HDL therapies.

Original languageEnglish
Article number101054
JournalNano Today
Volume36
ISSN1748-0132
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Adipose tissue browning
  • Atherosclerosis (AS) and type 2 diabetes
  • High-density lipoprotein mimetics
  • Peptide-derived nanoparticles

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