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

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 li-poprotein (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. (C) 2020 Published by Elsevier Ltd.

Automated summary

The peptide-based HDL (pHDL) constructed through microfluidics is a potential therapeutic candidate for managing dyslipidemia and hyperglycemia in atherosclerosis and type 2 diabetes. pHDL predominantly triggers activation of adipose tissue browning, providing new insights into its role in metabolic defects treatment.