Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model

Shu Niu; Shuchun Chen; Xing Chen; Qingjuan Ren; Lin Yue; Xiaoyu Pan; Huiying Zhao; Zelin Li; Xiaoyi Chen

doi:10.3389/fendo.2022.1046130

Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model

Front Endocrinol (Lausanne). 2022 Dec 9:13:1046130. doi: 10.3389/fendo.2022.1046130. eCollection 2022.

Authors

Shu Niu^{1

2}, Shuchun Chen^{1

3}, Xing Chen³, Qingjuan Ren², Lin Yue⁴, Xiaoyu Pan¹, Huiying Zhao², Zelin Li¹, Xiaoyi Chen¹

Affiliations

¹ Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
² Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China.
³ Department of Internal Medical, Hebei General Hospital, Shijiazhuang, Hebei, China.
⁴ Department of Endocrine, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

Abstract

Purpose: The aim of this study was to evaluate changes in body weight, liver weight, blood glucose, liver injury markers, pro-inflammatory factors and oxidative stress marker levels in obese mice with HFD induced NAFLD after semaglutide use.

Patients and methods: The 24 C57BL6J mice were randomly divided into three groups (NCD, HFD and Sema) for the assessment of metabolic status, inflammatory factor and oxidative stress marker levels, liver histopathology in mice. Liver metabolomics was determined by liquid chromatography/mass spectrometry (LC-MS) method.

Results: The mice body weight, liver weight, blood glucose, TG, TCHO, LDL and pro-inflammatory factors were significantly reduced after semaglutide. Meanwhile, semaglutide increased the SOD level. Semaglutide treatment significantly improved the pathological changes such as hepatocyte steatosis, balloon degeneration and lymphoid foci by HE. It also significantly reduced lipid droplet by Oil Red O. The mitochondria were swollen, the volume increased, the cristae were partially broken and reduced, the intramembrane matrix was partially dissolved, and the mitophagy structure was visible in the visual field. There were 6 metabolites down-regulated and 2 metabolites significantly up-regulated after semaglutide treatment.

Conclusions: Semaglutide can reduce blood glucose level and liver fat accumulation and play an anti-inflammatory role in advanced NAFLD that due to the effects of HFD.

Keywords: NAFLD; hepatic; hepatic fibrosis; metabolomics; semaglutide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Glucose
Body Weight
Diet, High-Fat / adverse effects
Disease Models, Animal
Mice
Non-alcoholic Fatty Liver Disease* / drug therapy
Non-alcoholic Fatty Liver Disease* / etiology
Non-alcoholic Fatty Liver Disease* / metabolism

Substances

semaglutide
Blood Glucose