Viscosol Treatment Ameliorates Insulin-Mediated Regulation of Dyslipidemia, Hepatic Steatosis, and Lipid Metabolism by Targeting PTP1B in Type-2 Diabetic Mice Model.

IF 2.3 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM International Journal of Endocrinology Pub Date : 2024-12-27 eCollection Date: 2024-01-01 DOI:10.1155/ije/3914332
Idrees Raza, Aamir Sohail, Hamza Muneer, Hajra Fayyaz, Zia Uddin, Amany I Almars, Waheeb S Aggad, Hailah M Almohaimeed, Imran Ullah
{"title":"Viscosol Treatment Ameliorates Insulin-Mediated Regulation of Dyslipidemia, Hepatic Steatosis, and Lipid Metabolism by Targeting PTP1B in Type-2 Diabetic Mice Model.","authors":"Idrees Raza, Aamir Sohail, Hamza Muneer, Hajra Fayyaz, Zia Uddin, Amany I Almars, Waheeb S Aggad, Hailah M Almohaimeed, Imran Ullah","doi":"10.1155/ije/3914332","DOIUrl":null,"url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein-tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti-inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of <i>Dodonaea viscosa</i>. Previously, we generated the high-fat diet (HFD)-low dose streptozotocin (STZ)-induced diabetic male mice model and treated it with a PTP1B inhibitor (5, 7-dihydroxy-3, 6-dimethoxy-2- (4-methoxy-3- (3-methyl-2-enyl) phenyl)-4H-chromen-4-one), isolated from Dodonaea viscosa. In the current study, we aimed to investigate the De novo lipogenesis, adipocyte differentiation, augmentation of lipoproteins clearance, fatty acid uptake, antilipolysis activity, and hepatic steatosis of PTP1B inhibition in adipose and liver tissues of the HFD-STZ-induced diabetic mice model. We found the retrieval of normal morphology of adipocytes and hepatocytes in the compound-treated group. The biochemical parameters showed the gradual reduction of LDL, VLDL, TC, and TG in the serum of the compound-treated group. To further test our hypothesis, real-time PCR was performed, and data revealed the reduction of PTP1B and other inflammatory markers in both tissues, showing enhanced expression of insulin signaling markers (INSR, IRS1, IRS2, and PI3K). Our compound upregulated the adipogenic (PPAR<i>γ</i>), lipogenic (SREBP1c, FAS, ACC, and DGAT2), lipoprotein clearance (LPL, LDLR, and VLDLR), fatty acid uptake (CD36 and FATP1), and lipid droplet forming (FSP27 and perilipin-1) markers expressions in adipocytes and downregulated in hepatocytes. Furthermore, we found elevated cholesterol efflux (in adipose and liver) and decreased lipolysis in adipocytes and elevated in hepatocytes. Hence, we can conclude that our compound protects the adipocytes from abrupt lipolysis and stimulates adipocyte differentiation. In addition, it plays a hepatic protective role by shifting clearance and uptake of lipoproteins and fatty acids to the peripheral tissues and retrieving the fatty liver condition.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2024 ","pages":"3914332"},"PeriodicalIF":2.3000,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698613/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/ije/3914332","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein-tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti-inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of Dodonaea viscosa. Previously, we generated the high-fat diet (HFD)-low dose streptozotocin (STZ)-induced diabetic male mice model and treated it with a PTP1B inhibitor (5, 7-dihydroxy-3, 6-dimethoxy-2- (4-methoxy-3- (3-methyl-2-enyl) phenyl)-4H-chromen-4-one), isolated from Dodonaea viscosa. In the current study, we aimed to investigate the De novo lipogenesis, adipocyte differentiation, augmentation of lipoproteins clearance, fatty acid uptake, antilipolysis activity, and hepatic steatosis of PTP1B inhibition in adipose and liver tissues of the HFD-STZ-induced diabetic mice model. We found the retrieval of normal morphology of adipocytes and hepatocytes in the compound-treated group. The biochemical parameters showed the gradual reduction of LDL, VLDL, TC, and TG in the serum of the compound-treated group. To further test our hypothesis, real-time PCR was performed, and data revealed the reduction of PTP1B and other inflammatory markers in both tissues, showing enhanced expression of insulin signaling markers (INSR, IRS1, IRS2, and PI3K). Our compound upregulated the adipogenic (PPARγ), lipogenic (SREBP1c, FAS, ACC, and DGAT2), lipoprotein clearance (LPL, LDLR, and VLDLR), fatty acid uptake (CD36 and FATP1), and lipid droplet forming (FSP27 and perilipin-1) markers expressions in adipocytes and downregulated in hepatocytes. Furthermore, we found elevated cholesterol efflux (in adipose and liver) and decreased lipolysis in adipocytes and elevated in hepatocytes. Hence, we can conclude that our compound protects the adipocytes from abrupt lipolysis and stimulates adipocyte differentiation. In addition, it plays a hepatic protective role by shifting clearance and uptake of lipoproteins and fatty acids to the peripheral tissues and retrieving the fatty liver condition.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
通过靶向 PTP1B,Viscosol 治疗可改善 2 型糖尿病小鼠模型中胰岛素介导的血脂异常、肝脏脂肪变性和脂质代谢调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
International Journal of Endocrinology
International Journal of Endocrinology ENDOCRINOLOGY & METABOLISM-
CiteScore
5.20
自引率
0.00%
发文量
147
审稿时长
1 months
期刊介绍: International Journal of Endocrinology is a peer-reviewed, Open Access journal that provides a forum for scientists and clinicians working in basic and translational research. The journal publishes original research articles, review articles, and clinical studies that provide insights into the endocrine system and its associated diseases at a genomic, molecular, biochemical and cellular level.
期刊最新文献
Viscosol Treatment Ameliorates Insulin-Mediated Regulation of Dyslipidemia, Hepatic Steatosis, and Lipid Metabolism by Targeting PTP1B in Type-2 Diabetic Mice Model. Angiotensin (1-7) Improves Pancreatic Islet Function via Upregulating PDX-1 and GCK: A Dose-Dependent Study in Mice. The Association Between Serum Uric Acid Levels and the Risk of Cognitive Dysfunction in Patients With Atrial Fibrillation. Efficacy of Local N-Acetylcysteine Administration in Mitigating OHSS Parameters: A Comparative Analysis With Dopaminergic Agonist in the OHSS Model. Interference Mechanisms of Endocrine System and Other Systems of Endocrine-Disrupting Chemicals in Cosmetics-In Vitro Studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1