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

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 remai...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511530/
https://www.ncbi.nlm.nih.gov/pubmed/34658856
http://dx.doi.org/10.3389/fphar.2021.713750
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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
author_facet 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
author_sort Yao, Minghe
collection PubMed
description 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.
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spelling pubmed-85115302021-10-14 Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice 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 Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-09-29 /pmc/articles/PMC8511530/ /pubmed/34658856 http://dx.doi.org/10.3389/fphar.2021.713750 Text en Copyright © 2021 Yao, Li, Huang, Tan, Shang, Meng, Pang, Xu, Zhao, Lei, Chang, Wang, Zhang, Zhang and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
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
Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title_full Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title_fullStr Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title_full_unstemmed Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title_short Sanye Tablet Ameliorates Insulin Resistance and Dysregulated Lipid Metabolism in High-Fat Diet-Induced Obese Mice
title_sort sanye tablet ameliorates insulin resistance and dysregulated lipid metabolism in high-fat diet-induced obese mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511530/
https://www.ncbi.nlm.nih.gov/pubmed/34658856
http://dx.doi.org/10.3389/fphar.2021.713750
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