{"title":"IDOL通过上调小鼠的UCP-1来减轻体重。","authors":"Hua Guan, Le Wang, Chengcheng Tang, Hao Xu, Aoqi Xiang, Xiaochang Chen, Qi Yu, Lixian Xu","doi":"10.1111/dom.16127","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Given the potential role of brown adipose tissue (BAT) in stimulating energy expenditure, activating BAT can be an effective anti-obesity treatment. Here, we aimed to use adenoviruses to establish the effect of the inducible degrader of the low density lipoprotein receptor (IDOL) in the formation of BAT.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>IDOL or green fluorescent protein was overexpressed by adenovirus and injected into the scapula of C57BL/6J mice and fed with high-fat diet for 12 weeks. We measured the body weight, morphology of lipid droplets, lipid profiles and adipogenesis protein expression levels. BAT was isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, we conducted western blot to verify the authenticity and reliability of the RNA sequencing results.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Compared with the control group, IDOL overexpression led to a significant reduction in body weight, consistent with the weight of adipose tissues and organs. Further studies show IDOL promotion increased ATGL, perilipin 1 and UCP-1 expression in BAT. However, perilipin 1 protein expression was significantly reduced in the Ad-IDOL group in epididymal white adipose tissue, while there was no significant difference in adiponectin, ATGL and perilipin 1 protein expression in inguinal white adipose tissue. Notably, serum FGF21 and leptin protein expression were negatively related to the adipose tissue decrease after Ad-IDOL administration. RNA sequencing analysis identified 1256 differentially expressed genes that were prominently enriched across nine signalling pathways. Additionally, the protein expression of PGAM2, G6PC1 and phosphorylation-AMPK was significantly increased after overexpression IDOL in BAT, which was consistent with the results of the RNA sequencing analysis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our research demonstrated that IDOL overexpression alleviates the body weight by promoting the phosphorylation of AMPK to upregulate the UCP-1 and ATGL exacerbating lipolysis in BAT.</p>\n </section>\n </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 3","pages":"1314-1326"},"PeriodicalIF":5.4000,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IDOL alleviates the body weight by upregulating UCP-1 in mice\",\"authors\":\"Hua Guan, Le Wang, Chengcheng Tang, Hao Xu, Aoqi Xiang, Xiaochang Chen, Qi Yu, Lixian Xu\",\"doi\":\"10.1111/dom.16127\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Given the potential role of brown adipose tissue (BAT) in stimulating energy expenditure, activating BAT can be an effective anti-obesity treatment. Here, we aimed to use adenoviruses to establish the effect of the inducible degrader of the low density lipoprotein receptor (IDOL) in the formation of BAT.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>IDOL or green fluorescent protein was overexpressed by adenovirus and injected into the scapula of C57BL/6J mice and fed with high-fat diet for 12 weeks. We measured the body weight, morphology of lipid droplets, lipid profiles and adipogenesis protein expression levels. BAT was isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, we conducted western blot to verify the authenticity and reliability of the RNA sequencing results.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Compared with the control group, IDOL overexpression led to a significant reduction in body weight, consistent with the weight of adipose tissues and organs. Further studies show IDOL promotion increased ATGL, perilipin 1 and UCP-1 expression in BAT. However, perilipin 1 protein expression was significantly reduced in the Ad-IDOL group in epididymal white adipose tissue, while there was no significant difference in adiponectin, ATGL and perilipin 1 protein expression in inguinal white adipose tissue. Notably, serum FGF21 and leptin protein expression were negatively related to the adipose tissue decrease after Ad-IDOL administration. RNA sequencing analysis identified 1256 differentially expressed genes that were prominently enriched across nine signalling pathways. Additionally, the protein expression of PGAM2, G6PC1 and phosphorylation-AMPK was significantly increased after overexpression IDOL in BAT, which was consistent with the results of the RNA sequencing analysis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our research demonstrated that IDOL overexpression alleviates the body weight by promoting the phosphorylation of AMPK to upregulate the UCP-1 and ATGL exacerbating lipolysis in BAT.</p>\\n </section>\\n </div>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\"27 3\",\"pages\":\"1314-1326\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-01-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/dom.16127\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/dom.16127","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
IDOL alleviates the body weight by upregulating UCP-1 in mice
Background
Given the potential role of brown adipose tissue (BAT) in stimulating energy expenditure, activating BAT can be an effective anti-obesity treatment. Here, we aimed to use adenoviruses to establish the effect of the inducible degrader of the low density lipoprotein receptor (IDOL) in the formation of BAT.
Methods
IDOL or green fluorescent protein was overexpressed by adenovirus and injected into the scapula of C57BL/6J mice and fed with high-fat diet for 12 weeks. We measured the body weight, morphology of lipid droplets, lipid profiles and adipogenesis protein expression levels. BAT was isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, we conducted western blot to verify the authenticity and reliability of the RNA sequencing results.
Results
Compared with the control group, IDOL overexpression led to a significant reduction in body weight, consistent with the weight of adipose tissues and organs. Further studies show IDOL promotion increased ATGL, perilipin 1 and UCP-1 expression in BAT. However, perilipin 1 protein expression was significantly reduced in the Ad-IDOL group in epididymal white adipose tissue, while there was no significant difference in adiponectin, ATGL and perilipin 1 protein expression in inguinal white adipose tissue. Notably, serum FGF21 and leptin protein expression were negatively related to the adipose tissue decrease after Ad-IDOL administration. RNA sequencing analysis identified 1256 differentially expressed genes that were prominently enriched across nine signalling pathways. Additionally, the protein expression of PGAM2, G6PC1 and phosphorylation-AMPK was significantly increased after overexpression IDOL in BAT, which was consistent with the results of the RNA sequencing analysis.
Conclusions
Our research demonstrated that IDOL overexpression alleviates the body weight by promoting the phosphorylation of AMPK to upregulate the UCP-1 and ATGL exacerbating lipolysis in BAT.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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