Liposome-encapsulated peptide PDBSN ameliorates high-fat-diet-induced obesity and improves metabolism homeostasis

https://doi.org/10.1016/j.bbrc.2020.09.014Get rights and content

Highlights

  • Previous study identified a peptide PDBSN restrict visceral adipocyte differentiation in vitro.

  • We encapsulated the peptide into liposomes attached with two ligands to improve stability and specificity.

  • Liposome-encapsulated peptide PDBSN ameliorates high-fat-diet-induced obesity and improves metabolism homeostasis.

Abstract

In recent years, the obese and overweight population has increased rapidly, which has become a worldwide public health problem. However, effective medication is lacking. Our previous study identified a novel peptide, PDBSN (GLSVADLAESIMKNL), that could significantly restrict adipocyte differentiation in vitro, but its in vivo function has not been determined. Thus, in this study, we encapsulated the peptide into liposomes attached with two ligands (visceral-adipose-tissue-targeting peptide and cell-penetrating peptide) to improve stability and specificity. We then tested the peptide’s function in HFD (high-fat diet)-induced obese mice and found that PDBSN could reduce weight gain and improve insulin resistance as well as lipid homeostasis. These results suggest that PDBSN may be a potential candidate for anti-obesity drug discovery.

Section snippets

Author contributions

Xirong GuoLiling XuDan shenJianfang GaoJia XiaXingyun WangYahui ZhouLing Chen

Synthesis and encapsulation of peptides

PDBSN (GLSVADLAESIMKNL) and the scramble peptide (MNAVSLELADLGSKI) used in this study were synthesized by Shanghai Scientific Peptide Biological Technology Co., Ltd.

The encapsulation of peptides was accomplished by Nanjing Nanoeast Biotech Co., Ltd. In brief, dissolve 60 mg PC (phosphatidylcholine) + 30 mg DSPE-PEG2000-COOH + 10 mg cholesterol into 4 ml chloroform, then to ensure it absolute solution through ultrasound. Next, rotating the solution at 70 °C to remove residual chloroform and form

ELISA

The ELISA kits for adiponectin (CSB-E07272 m) and leptin (CSB-E04650 m) were purchased from Wuhan Huamei Biotechnology Co., Ltd (Wuhan, China). The ELISA kits for IL-6 (4352) and TNF-α (7999) were purchased from Jiangsu MeiMian Industrial Co., Ltd (Yancheng, China).

Liposome encapsulation and modification increase peptide stability and specificity

To improve PDBSN characterizations in vivo, we designed a strategy by encapsulation of peptide into liposome (encapsulation efficiency (EE%): 63.14%) attached with cell-penetrated peptide (CPP) (encapsulation efficiency (EE%): 42.88%) and visceral adipose tissue targeting peptide (CGLHPAFQC) (encapsulation efficiency (EE%): 69.71%) [6](Fig. 1A). Then, the hydrodynamic size and zeta potential were analyzed using DLS (dynamic laser scatter) and results showed an effective coupling of peptide (

Discussion

On the basis of previous in vitro studies of the peptide PDBSN, we further encapsulated the peptide into liposomes attached to two ligands (targeting ligand and cell-penetrating peptide) in the present study. Then, the classic HFD-induced obese model was employed to study the in vivo function of PDBSN. Interestingly, PDBSN was enriched in adipose tissue, especially visceral fat, and reduced adipose mass and improved glucose metabolism as well as lipid homeostasis. Furthermore, the AMPK signal

Ethics approval

Animal studies were approved by the Ethics Committee of Shanghai sity (Number: 2019-097-01, Date: Dec. 20, 2019). All procedures were in accordance with the 3R (reduction, refinement, replacement) recommendations for ethical conduct of animal experimentation described in the Basel declaration (https://www.basel-declaration.org/basel-declaration/).

Consent for publication & competing interests

All authors agree to publish and confirm that there are no conflicts of interest.

Availability of data and materials

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of competing interest

All authors declare that there are no conflicts of interest about the article “Liposome-encapsulated peptide PDBSN ameliorates high-fat-diet-induced obesity and improves metabolism homeostasis”.

Acknowledgements and funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81670773), Nanjing Technological Development Program (201803012), Jiangsu provincial key research and development program (BE2018614), the 333 high level talents training project of Jiangsu Province.

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These authors contribute equally to this work.

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