lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Treatment of Obesity-Related Inflammation with a Novel Synthetic Pentacyclic Oleanane Triterpenoids via Modulation of Macrophages Polarization

42 Pages Posted: 17 Mar 2019

See all articles by Nanfei Yang

Nanfei Yang

Nanjing University

Qing Tang

Nanjing University

Wentao Qin

Nanjing University

Xiangyu Ge

Nanjing University

Dandan Wang

Nanjing University

Weijie Zhang

Nanjing University - Department of General Surgery

Yan Lu

Nanjing University

Zeyang Li

Peking University

Hongbin Sun

China Pharmaceutical University

Pingping Shen

Nanjing University - Drum Tower Hospital

More...

Abstract

Obesity leads to the chronic inflammation in the whole body and triggers the macrophage polarization to the pro-inflammatory phenotype. Targeting macrophage polarization provides a promising therapeutic strategy for obesity-related metabolic disorders and inflammation. Here, we show that SO1989, a derivative of natural occurring compound oleanolic acid, restores the balance between M1-polarized and M2-polarized macrophages in high fat diets (HFD)-induced obese mice resulting in the improvement of adipose inflammation and the metabolic dysfunctions. SO1989 exhibits similar or even stronger activity in inhibiting inflammation and M1 polarization of macrophages both in vitro and in vivo compared to its analogue CDDO-Me, previously known as a powerful anti-inflammation chemical small molecule. In addition, SO1989 can significantly increase the level of fatty acid oxidation in macrophages which can efficiently facilitate M2 polarization of macrophages. Unlike CDDO-Me, SO1989 shows lower adverse effects on adipose and appetite in mice. Taken all together, our findings identify SO1989 as a modulator in macrophage polarization and a safer potential leading compound for pro-resolution of inflammation treatment in metabolic disorders.

Funding: This research was financed by grants from the National Key Research and Development Plan (2017YFA0506000, 2017YFA0205400) and National Natural Science Foundation of China (81673439) and Natural Science Fund project in Jiangsu Province (BK20161408).

Declaration of Interest: The authors declare no conflict of interest.

Ethical Approval: Animal welfare and experimental procedures were followed in accordance with the Guide for Care and Use of Laboratory Animals (National Institutes of Health, the United States) and the related ethical regulations of Nanjing University.

Keywords: inflammation; macrophage polarization; SO1989; fatty acid oxidation; adverse effects

Suggested Citation

Yang, Nanfei and Tang, Qing and Qin, Wentao and Ge, Xiangyu and Wang, Dandan and Zhang, Weijie and Lu, Yan and Li, Zeyang and Sun, Hongbin and Shen, Pingping, Treatment of Obesity-Related Inflammation with a Novel Synthetic Pentacyclic Oleanane Triterpenoids via Modulation of Macrophages Polarization (March 15, 2019). EBioMedicine, Volume 45, July 2019, Pages 473-486, https://doi.org/10.1016/j.ebiom.2019.06.053, Available at SSRN: https://ssrn.com/abstract=3353367 or http://dx.doi.org/10.2139/ssrn.3353367

Nanfei Yang

Nanjing University

Nanjing, Jiangsu 210093
China

Qing Tang

Nanjing University

Nanjing, Jiangsu 210093
China

Wentao Qin

Nanjing University

Nanjing, Jiangsu 210093
China

Xiangyu Ge

Nanjing University

Nanjing, Jiangsu 210093
China

Dandan Wang

Nanjing University

Nanjing, Jiangsu 210093
China

Weijie Zhang

Nanjing University - Department of General Surgery ( email )

Nanjing
China

Yan Lu

Nanjing University

Nanjing, Jiangsu 210093
China

Zeyang Li

Peking University

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Hongbin Sun

China Pharmaceutical University ( email )

Nanjing Medical University
Jiangning
Nanjing, Jiangsu 211166
China

Pingping Shen (Contact Author)

Nanjing University - Drum Tower Hospital ( email )

321 Zhong Shan Road
Nanjing, Jiangning District 210008
China

Click here to go to TheLancet.com

Paper statistics

Abstract Views
178
Downloads
8