A peptide derived from the amino terminus of leptin improves glucose metabolism and energy homeostasis in myotubes and db/db mice.

IF 4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biological Chemistry Pub Date : 2024-10-25 DOI:10.1016/j.jbc.2024.107919
Mehmood Ali, Arvind Gupta, Rahul Dev Verma, Sariyah Akhtar, Jimut Kanti Ghosh
{"title":"A peptide derived from the amino terminus of leptin improves glucose metabolism and energy homeostasis in myotubes and db/db mice.","authors":"Mehmood Ali, Arvind Gupta, Rahul Dev Verma, Sariyah Akhtar, Jimut Kanti Ghosh","doi":"10.1016/j.jbc.2024.107919","DOIUrl":null,"url":null,"abstract":"<p><p>Leptin is an adipokine, which plays key roles in regulation of glucose-metabolism and energy-homeostasis. Therefore, identification of a short peptide from Leptin which improves glucose-metabolism and energy-homeostasis could be of significant therapeutic importance. Mutational studies demonstrated that N-terminal of human Leptin-hormone (LH) is crucial for activation of Leptin-receptor while its C-terminal seems to have lesser effects in it. Thus, for finding a metabolically active peptide and complimenting the mutational studies on Leptin, we have identified a 17-mer (Leptin-1) and a 16-mer (Leptin-2) segment from its N-terminal and C-terminal respectively. Consistent with the mutational studies, Leptin-1 improved glucose-metabolism by increasing glucose-uptake, GLUT4 expression and its translocation to the plasma-membrane in L6-myotubes, while Leptin-2 was mostly inactive. Leptin-1-induced glucose-uptake is mediated through activation of AMPK, PI3K and AKT proteins since inhibitors of these proteins inhibited the event. Leptin-1 activated leptin-receptor immediate downstream target protein, JAK2 reflecting its possible interaction with leptin-receptor while Leptin-2 was less active. Furthermore, Leptin-1 increased mitochondrial-biogenesis and ATP-production, and increased expression of PGC1α, NRF1 and Tfam proteins, that are important regulators of mitochondrial-biogenesis. The results suggested that Leptin-1 improved energy-homeostasis in L6-myotubes, whereas, Leptin-2 showed much lesser effects. In diabetic, db/db mice, Leptin-1 significantly decreased blood glucose level and improved glucose-tolerance. Leptin-1 also increased serum adiponectin and decreased serum TNF-α and IL-6 level signifying the improvement in insulin-sensitivity and decrease in insulin-resistance, respectively in db/db mice. Overall, the results show the identification of a short peptide from the N-terminal of human LH which significantly improves glucose-metabolism and energy-homeostasis.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biological Chemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jbc.2024.107919","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Leptin is an adipokine, which plays key roles in regulation of glucose-metabolism and energy-homeostasis. Therefore, identification of a short peptide from Leptin which improves glucose-metabolism and energy-homeostasis could be of significant therapeutic importance. Mutational studies demonstrated that N-terminal of human Leptin-hormone (LH) is crucial for activation of Leptin-receptor while its C-terminal seems to have lesser effects in it. Thus, for finding a metabolically active peptide and complimenting the mutational studies on Leptin, we have identified a 17-mer (Leptin-1) and a 16-mer (Leptin-2) segment from its N-terminal and C-terminal respectively. Consistent with the mutational studies, Leptin-1 improved glucose-metabolism by increasing glucose-uptake, GLUT4 expression and its translocation to the plasma-membrane in L6-myotubes, while Leptin-2 was mostly inactive. Leptin-1-induced glucose-uptake is mediated through activation of AMPK, PI3K and AKT proteins since inhibitors of these proteins inhibited the event. Leptin-1 activated leptin-receptor immediate downstream target protein, JAK2 reflecting its possible interaction with leptin-receptor while Leptin-2 was less active. Furthermore, Leptin-1 increased mitochondrial-biogenesis and ATP-production, and increased expression of PGC1α, NRF1 and Tfam proteins, that are important regulators of mitochondrial-biogenesis. The results suggested that Leptin-1 improved energy-homeostasis in L6-myotubes, whereas, Leptin-2 showed much lesser effects. In diabetic, db/db mice, Leptin-1 significantly decreased blood glucose level and improved glucose-tolerance. Leptin-1 also increased serum adiponectin and decreased serum TNF-α and IL-6 level signifying the improvement in insulin-sensitivity and decrease in insulin-resistance, respectively in db/db mice. Overall, the results show the identification of a short peptide from the N-terminal of human LH which significantly improves glucose-metabolism and energy-homeostasis.

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
一种源自瘦素氨基末端的多肽可改善肌管和 db/db 小鼠的葡萄糖代谢和能量平衡。
瘦素是一种脂肪因子,在调节葡萄糖代谢和能量平衡方面发挥着关键作用。因此,从瘦素中找出一种能改善糖代谢和能量平衡的短肽可能具有重要的治疗意义。突变研究表明,人类瘦素激素(LH)的 N 端是激活瘦素受体的关键,而其 C 端对瘦素受体的影响似乎较小。因此,为了找到具有代谢活性的多肽,并对瘦素的突变研究进行补充,我们分别从其 N 端和 C 端鉴定出了一个 17 聚体(瘦素-1)和一个 16 聚体(瘦素-2)片段。与突变研究一致的是,Leptin-1 通过增加 L6 肌细胞的葡萄糖摄取、GLUT4 表达及其向血浆膜的转运,改善了葡萄糖代谢,而 Leptin-2 则大多没有活性。瘦素-1诱导的葡萄糖摄取是通过激活 AMPK、PI3K 和 AKT 蛋白介导的,因为这些蛋白的抑制剂抑制了这一过程。瘦素-1能激活瘦素受体的直接下游靶蛋白JAK2,这反映了它可能与瘦素受体相互作用,而瘦素-2的活性较低。此外,瘦素-1 增加了线粒体生物生成和 ATP 生成,并增加了 PGC1α、NRF1 和 Tfam 蛋白的表达,这些蛋白是线粒体生物生成的重要调节因子。结果表明,Leptin-1 能改善 L6 肌细胞的能量平衡,而 Leptin-2 的作用则要小得多。在糖尿病 db/db 小鼠中,Leptin-1 能显著降低血糖水平并改善糖耐量。Leptin-1还能增加血清脂肪连素,降低血清TNF-α和IL-6水平,这表明Leptin-1能分别改善糖尿病小鼠的胰岛素敏感性和胰岛素抵抗性。总之,研究结果表明,从人类 LH 的 N 端鉴定出的短肽能显著改善葡萄糖代谢和能量平衡。
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
Journal of Biological Chemistry
Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry
自引率
4.20%
发文量
1233
期刊介绍: The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.
期刊最新文献
Substrate specificity and kinetic mechanism of 3-hydroxy-Δ5-C27-steroid oxidoreductase. ARMC5 selectively degrades SCAP-free SREBF1 and is essential for fatty acid desaturation in adipocytes. FREE FATTY ACIDS INHIBIT AN ION-COUPLED MEMBRANE TRANSPORTER BY DISSIPATING THE ION GRADIENT. O-GlcNAcylation of RPA2 at S4/S8 antagonizes phosphorylation and regulates checkpoint activation during replication stress. Oligomerization of Protein Arginine Methyltransferase 1 and Its Functional Impact on Substrate Arginine Methylation.
×
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