Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice

Author:

Yao Minghe,Li Lin,Huang Ming,Tan Yao,Shang Ye,Meng Xianghui,Pang Yafen,Xu Hong,Zhao Xin,Lei Wei,Chang Yanxu,Wang Yi,Zhang Deqin,Zhang Boli,Li Yuhong

Abstract

Sanye Tablet (SYT) is a patent prescription widely used in treating T2D and pre-diabetes, especially T2D comorbid with hypertriglyceridemia, for many years in China. However, the underlying mechanism that accounts for the anti-diabetic potential of SYT by regulating lipid-related intermediates remains to be elucidated. This study aimed to investigate the mechanism of SYT on lipid metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice by means of combining lipidomics and proteomics. The obese mice models were developed via HFD feeding for 20 consecutive weeks. Mice in the treatment group were given metformin and SYT respectively, and the effects of SYT on body weight, blood glucose, insulin sensitivity, fat accumulation in the organs, and pathological changes in the liver were monitored. Lipid metabolism was examined by lipidomics. Further determination of signaling pathways was detected by proteomics. The biological contributions of the compounds detected in SYT’s chemical fingerprint were predicted by network pharmacology. SYT treatment reduced body weight, inhibited viscera and hepatic steatosis lipid accumulation, and prevented insulin resistance. Furthermore, it was found that circulatory inflammatory cytokines were reduced by SYT treatment. In addition, lipidomics analysis indicated that SYT targets lipid intermediates, including diacylglycerol (DAG) and Ceramide (Cer). Mechanistically, SYT positively affected these lipid intermediates by suppressing liver lipogenesis via downregulation of SREBP1/ACC and the JAK/STAT signaling pathway. Our results predicted that astragalin and rosmarinic acid might regulate the JAK-STAT pathway by targeting PIM2 and STAT1, respectively, while paeoniflorin and rosmarinic acid were likely to regulate inflammatory responses by targeting TNFα, IL-6, and IL-4 during T2D. Overall, our study provides supportive evidence for the mechanism of SYT’s therapeutic effect on dysregulated lipid metabolism in diabesity.

Funder

Foundation for Innovative Research Groups of the National Natural Science Foundation of China

Natural Science Foundation of Tianjin City

Publisher

Frontiers Media SA

Subject

Pharmacology (medical),Pharmacology

Reference45 articles.

1. Interleukin-1α Deficiency Reduces Adiposity, Glucose Intolerance and Hepatic De-novo Lipogenesis in Diet-Induced Obese Mice;Almog;BMJ. Open. Diabetes Res. Care,2019

2. Triglyceride Accumulation: Inhibitory Effects of Tangzhiqing Formula;An;Altern. Ther. Health Med.,2013

3. Obesity, Insulin Resistance and Free Fatty Acids;Boden;Curr. Opin. Endocrinol. Diabetes Obes.,2011

4. Role of Sphingolipid Mediator Ceramide in Obesity and Renal Injury in Mice Fed a High-Fat Diet;Boini;J. Pharmacol. Exp. Ther.,2010

5. Plasma Sphingolipids Are Biomarkers of Metabolic Syndrome in Non-human Primates Maintained on a Western-Style Diet;Brozinick;Int. J. Obes. (Lond),2013

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3