• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

线粒体衍生肽 SHLP2 通过激活下丘脑神经元来调节能量平衡。

Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

机构信息

Division of Physiology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, 03722, Korea.

Department of Applied Life Science, BK21 FOUR, Yonsei University College of Dentistry, Seoul, 03722, Korea.

出版信息

Nat Commun. 2023 Jul 19;14(1):4321. doi: 10.1038/s41467-023-40082-7.

DOI:10.1038/s41467-023-40082-7
PMID:37468558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10356901/
Abstract

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.

摘要

小分子人类似肽 2 (SHLP2) 是一种线粒体衍生肽，参与多种生物学过程，如衰老和氧化应激。然而，其在调节能量平衡中的功能作用尚不清楚，其相应的受体也未被鉴定。在此，我们证明了全身和脑室内 (ICV) 给予 SHP2 均可保护雄性小鼠免受高脂肪饮食 (HFD) 诱导的肥胖，并改善胰岛素敏感性。此外，SHLP2 在下丘脑弓状核 (ARC) 中激活 pro-opiomelanocortin (POMC) 神经元可抑制摄食并促进产热。通过高通量结构互补筛选，我们发现 SHP2 与趋化因子受体 7 (CXCR7) 结合并激活其。综上所述，我们的研究不仅揭示了 SHP2 在代谢紊乱中的治疗潜力，还为其对能量平衡的作用机制提供了重要的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/76ce4ee437e9/41467_2023_40082_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/1a9387b6c1d4/41467_2023_40082_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/966d0dbb3cd9/41467_2023_40082_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/2be9bb30ba6a/41467_2023_40082_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/76ec7fe56574/41467_2023_40082_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/1de97b0b1d39/41467_2023_40082_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/76ce4ee437e9/41467_2023_40082_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/1a9387b6c1d4/41467_2023_40082_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/966d0dbb3cd9/41467_2023_40082_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/2be9bb30ba6a/41467_2023_40082_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/76ec7fe56574/41467_2023_40082_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/1de97b0b1d39/41467_2023_40082_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9e0/10356901/76ce4ee437e9/41467_2023_40082_Fig6_HTML.jpg

相似文献

1
Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.线粒体衍生肽 SHLP2 通过激活下丘脑神经元来调节能量平衡。
Nat Commun. 2023 Jul 19;14(1):4321. doi: 10.1038/s41467-023-40082-7.
2
Overexpression of Smad7 in hypothalamic POMC neurons disrupts glucose balance by attenuating central insulin signaling.下丘脑 POMC 神经元中 Smad7 的过表达通过减弱中枢胰岛素信号传导破坏葡萄糖平衡。
Mol Metab. 2020 Dec;42:101084. doi: 10.1016/j.molmet.2020.101084. Epub 2020 Sep 22.
3
Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice.胰岛淀粉样多肽受体不敏感会损害母鼠高脂肪饮食喂养雄性子代下丘脑 POMC 神经元的分化。
Mol Metab. 2021 Feb;44:101135. doi: 10.1016/j.molmet.2020.101135. Epub 2020 Dec 3.
4
Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.Sirt6 在 pro-opiomelanocortin 神经元中通过调节瘦素信号来控制能量代谢。
Mol Metab. 2020 Jul;37:100994. doi: 10.1016/j.molmet.2020.100994. Epub 2020 Apr 9.
5
Hypothalamic Pomc expression restricted to GABAergic neurons suppresses Npy overexpression and restores food intake in obese mice.下丘脑 Pomc 表达仅限于 GABA 能神经元可抑制 Npy 过表达并恢复肥胖小鼠的食物摄入。
Mol Metab. 2020 Jul;37:100985. doi: 10.1016/j.molmet.2020.100985. Epub 2020 Apr 18.
6
Centrally circulating α-klotho inversely correlates with human obesity and modulates arcuate cell populations in mice.循环血中α-klotho 与肥胖呈负相关，并调节肥胖小鼠弓状核细胞群。
Mol Metab. 2021 Feb;44:101136. doi: 10.1016/j.molmet.2020.101136. Epub 2020 Dec 7.
7
Sestrin2 in POMC neurons modulates energy balance and obesity related metabolic disorders via mTOR signaling.POMC 神经元中的 sestrin2 通过 mTOR 信号调节能量平衡和肥胖相关代谢紊乱。
J Nutr Biochem. 2024 Nov;133:109703. doi: 10.1016/j.jnutbio.2024.109703. Epub 2024 Jul 25.
8
Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity.线粒体 OXPHOS 轻度损伤促进 POMC 神经元中脂肪酸的利用，并改善肥胖症中的葡萄糖稳态。
Cell Rep. 2018 Oct 9;25(2):383-397.e10. doi: 10.1016/j.celrep.2018.09.034.
9
Nociceptin/orphanin FQ modulates energy homeostasis through inhibition of neurotransmission at VMN SF-1/ARC POMC synapses in a sex- and diet-dependent manner.孤啡肽/神经激肽 FQ 通过抑制 VMN SF-1/ARC POMC 突触中的神经传递，以一种依赖于性别和饮食的方式调节能量稳态。
Biol Sex Differ. 2019 Feb 12;10(1):9. doi: 10.1186/s13293-019-0220-3.
10
Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.Alx3 缺乏会破坏能量平衡，改变身体成分，并损害下丘脑对食物摄入的调节。
Cell Mol Life Sci. 2024 Aug 12;81(1):343. doi: 10.1007/s00018-024-05384-z.

引用本文的文献

1
Multitissue single-cell analysis reveals differential cellular and molecular sensitivity between fructose and high-fat high-sucrose diets.多组织单细胞分析揭示了果糖与高脂肪高糖饮食之间不同的细胞和分子敏感性。
Cell Rep. 2025 May 27;44(5):115690. doi: 10.1016/j.celrep.2025.115690. Epub 2025 May 10.
2
Eukaryotic Microproteins.真核生物微小蛋白
Annu Rev Biochem. 2025 Jun;94(1):1-28. doi: 10.1146/annurev-biochem-080124-012840. Epub 2025 Apr 17.
3
The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.

本文引用的文献

1
Hypothalamic control of energy expenditure and thermogenesis.下丘脑对能量消耗和产热的控制。
Exp Mol Med. 2022 Apr;54(4):358-369. doi: 10.1038/s12276-022-00741-z. Epub 2022 Mar 17.
2
The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.线粒体衍生肽 MOTS-c 可缓解妊娠期糖尿病的高血糖和胰岛素抵抗。
Pharmacol Res. 2022 Jan;175:105987. doi: 10.1016/j.phrs.2021.105987. Epub 2021 Nov 17.
3
Hypothalamic primary cilium: A hub for metabolic homeostasis.下丘脑初级纤毛：代谢稳态的枢纽。
阿尔茨海默病及相关痴呆中血管功能障碍与tau蛋白病之间的相互作用。
Alzheimers Dement. 2025 Feb;21(2):e14618. doi: 10.1002/alz.14618.
4
A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.人胰岛素肽及其类似物在调节自噬途径以治疗代谢紊乱中的潜在作用综述
Protein Pept Lett. 2025;32(3):161-170. doi: 10.2174/0109298665363711250112050930.
5
Traditional Chinese Medicine Treats Obesity by Regulating the Central Nervous System via Short-chain Fatty Acids.中医通过短链脂肪酸调节中枢神经系统治疗肥胖症。
Curr Pharm Des. 2025;31(21):1710-1719. doi: 10.2174/0113816128354909241213070313.
6
Mitochondrial-derived microproteins: from discovery to function.线粒体衍生的微小蛋白质：从发现到功能
Trends Genet. 2025 Feb;41(2):132-145. doi: 10.1016/j.tig.2024.11.010. Epub 2024 Dec 16.
7
Socialized mitochondria: mitonuclear crosstalk in stress.社会化的线粒体：应激中的线粒体-核互作
Exp Mol Med. 2024 May;56(5):1033-1042. doi: 10.1038/s12276-024-01211-4. Epub 2024 May 1.
8
AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation.AGP1 在 POMC 神经元中通过瘦素介导的 STAT3 磷酸化调节能量平衡和代谢。
Nat Commun. 2024 Apr 20;15(1):3377. doi: 10.1038/s41467-024-47684-9.
9
Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.线粒体衍生肽：抗糖尿病功能及进化观点。
Peptides. 2024 Feb;172:171147. doi: 10.1016/j.peptides.2023.171147. Epub 2023 Dec 29.
10
Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.人胰岛素及其类似物的神经保护作用：研究发现与展望
Biology (Basel). 2023 Dec 16;12(12):1534. doi: 10.3390/biology12121534.
Exp Mol Med. 2021 Jul;53(7):1109-1115. doi: 10.1038/s12276-021-00644-5. Epub 2021 Jul 1.
4
Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting.通过交叠靶向揭示下丘脑中功能不同的 POMC 表达神经元亚群。
Nat Neurosci. 2021 Jul;24(7):913-929. doi: 10.1038/s41593-021-00854-0. Epub 2021 May 17.
5
The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.黑素皮质素途径与能量稳态：从发现到肥胖治疗。
Mol Metab. 2021 Jun;48:101206. doi: 10.1016/j.molmet.2021.101206. Epub 2021 Mar 6.
6
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.MOTS-c 是一种运动诱导的线粒体编码调节因子，可调节与年龄相关的身体衰退和肌肉内稳态。
Nat Commun. 2021 Jan 20;12(1):470. doi: 10.1038/s41467-020-20790-0.
7
CXCR7: a β-arrestin-biased receptor that potentiates cell migration and recruits β-arrestin2 exclusively through Gβγ subunits and GRK2.CXCR7：一种偏向β-抑制蛋白的受体，可增强细胞迁移，并仅通过Gβγ亚基和GRK2募集β-抑制蛋白2。
Cell Biosci. 2020 Nov 23;10(1):134. doi: 10.1186/s13578-020-00497-x.
8
Ventromedial hypothalamic primary cilia control energy and skeletal homeostasis.下丘脑腹内侧核初级纤毛控制能量和骨骼稳态。
J Clin Invest. 2021 Jan 4;131(1). doi: 10.1172/JCI138107.
9
Leptin, Obesity, and Hypertension: A Review of Pathogenetic Mechanisms.瘦素、肥胖与高血压：发病机制的综述。
Metab Syndr Relat Disord. 2020 Nov;18(9):399-405. doi: 10.1089/met.2020.0065. Epub 2020 Sep 1.
10
Mitochondrial-derived peptides in energy metabolism.线粒体衍生肽在能量代谢中的作用。
Am J Physiol Endocrinol Metab. 2020 Oct 1;319(4):E659-E666. doi: 10.1152/ajpendo.00249.2020. Epub 2020 Aug 10.