Our study is the first to use genipin, a naturally occurring collagen cross-linking agent, as a therapeutic agent to treat superficial digital flexor tendon (SDFT) injuries in horses. The promising approach of intratendinous genipin injection and tendon mechanical enhancement could be a viable alternative to current therapies for SDFT injuries.

开始日期2016-06-28

申办/合作机构

University of Zurich

100 项与 Mitochondrial uncoupling proteins 相关的临床结果

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100 项与 Mitochondrial uncoupling proteins 相关的转化医学

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0 项与 Mitochondrial uncoupling proteins 相关的专利（医药）

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项与 Mitochondrial uncoupling proteins 相关的文献（医药）

2025-01-01·Journal of Ethnopharmacology

Eriodictyol regulates white adipose tissue browning and hepatic lipid metabolism in high fat diet-induced obesity mice via activating AMPK/SIRT1 pathway

Article

作者: Liu, Qiang ; Cai, Wei-Feng ; Yi, Yan-Kui ; Ni, Qian ; Li, Xiao-Yi ; Shen, Chun-Yan ; Chen, Qi-Cong ; Jiang, Cui-Ping ; Liu, Li ; Lin, Song-Xia

ETHNOPHARMACOLOGICAL RELEVANCEBlossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive.AIM OF THE STUDYThis study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight.MATERIALS AND METHODSThe pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, Western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins.RESULTSIn vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted.CONCLUSIONEriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.

2025-01-01·Biochimica et Biophysica Acta (BBA) - Bioenergetics

In isolated brown adipose tissue mitochondria, UCP1 is not essential for - nor involved in - the uncoupling effects of the classical uncouplers FCCP and DNP

Article

作者: Jiménez, Beatriz ; Sousa-Filho, Celso Pereira Batista ; Shabalina, Irina G. ; Nedergaard, Jan ; Shabalina, Irina G ; Cannon, Barbara

Recent patch-clamp studies of mitoplasts have challenged the traditional view that classical chemical uncoupling (by e.g. FCCP or DNP) is due to the protonophoric property of these substances themselves. These studies instead suggest that in brown-fat mitochondria, FCCP- and DNP-induced uncoupling is mediated through activation of UCP1 (and in other tissues by activation of the adenine nucleotide transporter). These studies thus advocate an entirely new paradigm for the interpretation of standard bioenergetic experiments. To examine whether these patch-clamp results obtained in brown-fat mitoplasts are directly transferable to classical isolated brown-fat mitochondria studies, we investigated the effects of FCCP and DNP in brown-fat mitochondria from wildtype and UCP1 KO mice, comparing the FCCP and DNP effects with those of a fatty acid (oleate), a bona fide activator of UCP1. Whereas the sensitivity of brown-fat mitochondria to oleate was much higher in UCP1-containing than in UCP1 KO mitochondria, there was no difference in sensitivity to FCCP and DNP between these mitochondria, neither in oxygen consumption rate nor in membrane potential studies. Correspondingly, the UCP1-dependent ability of GDP to competitively inhibit activation by oleate was not seen with FCCP and DNP. It would thus be premature to abandon the established bioenergetic interpretation of chemical uncoupler effects in classical isolated brown-fat mitochondria-and probably also generally in this type of mitochondrial study. Understanding the molecular and structural reasons for the different outcomes of mitoplast and mitochondrial studies is a challenging task.

2025-01-01·Journal of Ethnopharmacology

Integrating network pharmacology and transcriptomics to study the potential mechanism of Jingzhi Niuhuang Jiedu tablet in rats with accumulation of heat in the lungs and stomach

Article

作者: Xu, Bing ; Li, Shan-Lan ; Gu, Yu-Hao ; Guo, Zhuo-Qian ; Gu, Yu-hao ; Lei, Hai-min ; Lin, Yi-xuan ; Gao, Feng ; Zhao, Shu-Wu ; Yan, Ying ; Dai, Zi-Qi ; Chu, Ya-fen ; Dai, Zi-qi ; Zhang, Tong ; Jiao, Jing-yi ; Chu, Ya-Fen ; Lin, Yi-Xuan ; Lei, Hai-Min ; Li, Shan-lan ; Zhao, Shu-wu ; Guo, Zhuo-qian ; Jiao, Jing-Yi

ETHNOPHARMACOLOGICAL RELEVANCEAccumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored.AIM OF THE STUDYThe objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS.MATERIALS AND METHODSThe effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1.RESULTSWe identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1β, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1).CONCLUSIONThis study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.

项与 Mitochondrial uncoupling proteins 相关的新闻（医药）

2024-09-30

·生物谷

「枸杞泡水」到底灵不灵？科学研究证实：枸杞子不仅可以促进白色脂肪组织米色化，增加能量消耗、增强产热功能，还能抗衰老、强筋健骨！

“人到中年不得已，保温杯里泡枸杞”，这句话已经成了很多人的日常调侃。随着健康养生观念的提升，无论是年轻人还是中老年人，枸杞水俨然成了许多人日常保健的“标配”。（你爱不爱喝枸杞泡水？快去文末投票哦！）图片来源自千库网那么，枸杞真的这么神奇吗？其实，枸杞作为传统名贵中药，早在两千多年前就被《神农本草经》列为“上品”，《本草纲目》更有记载它“久服坚筋骨，轻身不老，耐寒暑”的功效。而如今，科学家们的研究进一步证实了枸杞的神奇功效。最新研究表明，枸杞多糖（Lycium barbarum polysaccharide，简称LBP）通过调节肠道菌群，显著增强人体的产热作用和能量代谢，从而帮助抵抗寒冷。这一发现不仅让我们对枸杞有了更深的科学认识，也为如何提升人体的耐寒力提供了新的方向。这不禁让我们感慨，老祖宗的智慧再次被现代科学所验证，枸杞真的不只是“网红养生品”，它有着深厚的科学依据！近日，中国科学院生物物理研究所陈畅研究组与中国科学院上海药物研究所丁侃研究组合作，在《The FASEB Journal》杂志在线发表了题为"Lycium barbarum polysaccharide increases thermogenesis and energy metabolism through modulation of the gut microbiota to confer resistance to cold temperatures"的研究论文[1]，该研究首次揭示了枸杞子通过促进白色脂肪组织的米色化及增强机体产热能力，以对抗冷应激，从而实现其传统上被认为具有的“耐寒暑”功效。此项研究全面解析了枸杞子“耐寒暑”功效背后的科学机制，为这一古老药材的功效提供了现代科学的解释。枸杞多糖是“耐寒暑”功效的关键该团队采用了C57BL/6小鼠作为模型，研究了枸杞多糖对抗寒能力的影响。小鼠被分为实验组与对照组，实验组长期摄入枸杞多糖。具体而言，研究团队首先通过冷环境暴露实验，观察小鼠的核心体温变化，利用代谢笼监测两组小鼠的能量消耗情况。结果表明，枸杞多糖能够显著提高白色脂肪组织中棕色化标志物的表达，增强产热能力。此外，研究人员通过免疫组化和Western Blot技术发现，枸杞多糖可以显著激活棕色脂肪组织中的UCP1蛋白，促进产热并增加代谢率。更进一步的机制研究揭示了枸杞多糖在肠道菌群层面的作用。16S rRNA测序分析表明，枸杞多糖的补充显著增加了小鼠肠道菌群中Bacteroidetes的丰度，降低了Firmicutes/Bacteroidetes的比例。图：LBP调控提高产热和能量代谢以增强耐寒能力的模式图，图片来源自[1] 此外，短链脂肪酸（SCFA）产生菌如Lachnospiraceae、Ruminococcaceae和Bacteroidaceae的丰度也有所增加，这些菌群能够提升短链脂肪酸的水平，进一步促进肠道健康和代谢功能。研究还发现，枸杞多糖增加了小鼠体内肠道GLP-1的释放，该激素通过激活小鼠白色脂肪组织中的CREB/PGC1α信号通路，促进能量消耗并增强产热功能。通过这一系列精密的实验分析，研究揭示了枸杞多糖通过调节肠道菌群、提升肠道激素水平来实现产热和能量消耗的机制。令人兴奋的是，这项研究首次科学地解释了传统中药中“耐寒暑”功效的机制，为进一步理解其它类似中药的作用机制提供了参考依据，同时也暗示枸杞多糖有望成为高寒地区人群的安全膳食补充剂。无需运动，枸杞提取物就能够改善肌肉耐力！枸杞的神奇功效不仅局限于提升耐寒能力。近年来，该团队关于枸杞提取物的研究在多个领域取得了显著进展。例如，研究表明，枸杞提取物能够通过激活ERRγ信号通路，模拟运动效果，增加IIa型氧化肌纤维，从而改善肌肉耐力。探索其有效成分时发现柚皮素（Naringenin，NAR）作用显著，NAR能在形态学和功能上显著挽救肌肉损伤，发现其在缓解衰老过程或疾病相关的肌肉萎缩方面的重要作用。这些发现表明，枸杞提取物能够在无需运动的情况下，帮助人体提升肌肉的氧化能力，类似于长期锻炼带来的效果[2,3]。图：柚皮素（NAR）可提高肌肉耐力，防止与疾病相关的肌肉萎缩，图片来源自[3] 不止如此，枸杞提取物还能“坚筋骨”+“抗衰老”！此外，枸杞提取物LBP1C-2还能够通过与成纤维细胞生长因子受体1（FGFR1）相互作用，保持骨骼肌卫星细胞的数量，帮助维持肌肉再生功能[4]。另一项相关研究还发现，LBP1C-2能够通过靶向BMPRIA/BMPRII/Noggin通路，缓解年龄相关的骨质流失，进一步证实了枸杞提取物在抗衰老和骨骼健康方面的巨大潜力[5]。由此可见，枸杞不仅“耐寒暑”，在“坚筋骨”和“抗衰老”方面也同样功不可没。小结从古至今，枸杞作为中华传统文化中的瑰宝，数千年来被用于医药和保健。《神农本草经》和《本草纲目》中的记载再一次被现代科学所验证！枸杞的功效不仅是古代智慧的象征，更是现代科学的崭新发现。枸杞所含的多糖、提取物等成分，不仅能够增强产热能力、提升能量代谢和耐寒性，还在肌肉、骨骼等方面展现了巨大的潜力。这些研究成果无不昭示着中华民族几千年来积累下来的医药知识在当今科学领域焕发出新的光彩。所以，泡一杯枸杞水，已经不再只是“人到中年”的无奈，而是健康生活的明智选择。无论是年轻人还是老年人，枸杞都能成为你日常保健的好伙伴。用老祖宗的智慧来呵护健康，不仅简单实用，还很有文化自信！冬天来了，不妨给自己泡上一杯枸杞茶，让这古老的中药带给你暖暖的能量和健康的呵护。谁知道呢？也许你的保温杯里，真的藏着延续几千年的健康密码咧！参考文献： [1] Sun C, Su J, Wang J, Ding K, Chen C. Lycium barbarum polysaccharide increases thermogenesis and energy metabolism through modulation of the gut microbiota to confer resistance to cold temperatures. FASEB J. 2024;38(17):e70010. [2] Meng J, Lv Z, Sun C, Qiao X, Chen C. An extract of Lycium barbarum mimics exercise to improve muscle endurance through increasing type IIa oxidative muscle fibers by activating ERRγ. FASEB J. 2020;34(9):11460-11473. [3] Lv Z, Meng J, Yao S, et al. Naringenin improves muscle endurance via activation of the Sp1-ERRγ transcriptional axis. Cell Rep. 2023;42(11):113288. [4] Meng J, Lv Z, Chen X, et al. LBP1C-2 from Lycium barbarum maintains skeletal muscle satellite cell pool by interaction with FGFR1. iScience. 2023;26(5):106573. [5] Sun C, Chen X, Yang S, Jin C, Ding K, Chen C. LBP1C-2 from Lycium barbarum alleviated age-related bone loss by targeting BMPRIA/BMPRII/Noggin. Carbohydr Polym. 2023;310:120725. 撰文 | Shawn 编辑 | lcc 部分文字来源于网络，本文仅用于分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！精彩推荐： 1、你是哪一派？「发烧马上吃退烧药」or「熬一熬，让身体“自愈”」研究表明：发烧并非一件坏事，它是一种有利的免疫机制 2、藏红花素竟能逆转衰老，延长寿命！最新研究：藏红花素通过提升细胞能量，延缓大脑和身体老化 3、运动时长 or 运动强度哪个才是关键？最新研究：高强度比长时间运动更能带来健康益处，并且将高强度活动集中在较短时间内进行更有效 4、人有三千烦恼丝，奈何只剩一千五？最新研究发现：多吃外卖、多喝瓶装水更易脱发！微塑料会对皮肤和毛囊造成显著损伤，甚至导致脱发！ 5、喝咖啡全是好处？Nature“颠覆性”研究：咖啡饮用量与肺癌风险之间存在显著正相关性，每天多喝1杯咖啡，罹患肺癌的风险增加6%！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

微生物疗法

2024-09-10

·生物探索

Cell Metab丨肖玲等揭示棕色脂肪中的m⁶A mRNA甲基化通过独立于UCP1的前列腺素信号调控全身胰岛素敏感性

引言棕色脂肪组织（BAT）因其通过解偶联蛋白1（UCP1）产生热量，成为治疗和预防肥胖及相关代谢疾病的潜在靶点。研究表明，冷刺激激活的BAT可以通过能量消耗减少体脂，改善心脏代谢健康，特别在超重和肥胖个体中效果显著。尽管BAT的产热功能备受关注，近年来越来越多的证据表明，BAT还通过分泌各种有益因子（"BATokine"，如肽类、蛋白质、脂质、miRNA等）对全身代谢产生积极调节。其中，一类被称为“BAT lipokine”的脂质因子尤为重要【1,2】，它与胰岛素敏感性、葡萄糖耐量以及炎症调节密切相关。 m6A（N6-甲基腺嘌呤）是RNA中最常见的内部甲基化修饰之一，广泛存在于真核生物的mRNA和非编码RNA中，在RNA剪接、翻译、稳定性和降解等过程中发挥重要作用。m6A修饰与干细胞分化、肿瘤发生、免疫调控和代谢紊乱等生理与病理过程密切相关。尽管已知m6A在棕色脂肪产热中具有重要作用，但m6A是否通过调控棕色脂肪分泌的"BATokine"影响全身代谢尚不清楚。 2024年9月9日，哈佛医学院及Joslin糖尿病研究中心（Joslin Diabetes Center）的Rohit N. Kulkarni教授团队在Cell Metabolism在线发表了题为m6A mRNA Methylation in Brown Fat Regulates Systemic Insulin Sensitivity via an Inter-Organ Prostaglandin Signaling Axis Independent of UCP1的研究成果。该研究通过基因组学、甲基化组学和脂质组学等多组学手段，首次揭示了：1. 由甲基转移酶14（METTL14）介导的m6A修饰，通过负向调控BAT中前列腺素合成酶的表达，抑制了前列腺素PGE2和PGF2α的合成；2. 敲除BAT中的METTL14显著提高了PGE2和PGF2α的水平，从而改善了胰岛素敏感性，促进了白色脂肪棕色化，并降低了肥胖小鼠体重；3. 揭示了PGE2和PGF2α作为新型胰岛素增敏剂的新分子机制。研究者首先检测了不同胰岛素抵抗小鼠模型中BAT的m6A甲基转移酶水平，发现胰岛素抵抗小鼠BAT中METTL14高表达，提示其与胰岛素敏感性负相关。进一步通过特异性敲除小鼠BAT中的METTL14，结果显示，敲除后小鼠全身多种代谢组织的胰岛素敏感性显著提升。这表明METTL14的缺失能够通过BAT与其他代谢组织的相互作用改善胰岛素敏感性，且不依赖于UCP1的产热功能。通过脂质组学分析，研究者发现，在METTL14缺失的小鼠棕色脂肪组织及人源性棕色脂肪细胞中，PGE2和PGF2α的水平显著升高。进一步研究表明，PGE2和PGF2α能够显著增强代谢细胞的胰岛素敏感性。在肥胖小鼠模型中注射这两种前列腺素，表现出胰岛素增敏及抗肥胖的表型特征，并伴随白色脂肪组织的米色化现象。值得注意的是，PGE2和PGF2α的血液水平在肥胖及胰岛素抵抗人体中与胰岛素敏感性呈显著正相关。机制研究进一步揭示，PGE2和PGF2α通过特异性GPCR介导的信号通路，抑制AKT磷酸酶的活性，从而提高胰岛素敏感性。模式图（Credit: Cell Metabolism）为了进一步研究m6A如何调控BAT中前列腺素的合成，研究者结合基因组学和m6A甲基化组学，发现METTL14的缺失通过降低m6A甲基化水平，增强了前列腺素合成酶基因的稳定性，增加了其表达。综上所述，该研究揭示了m6A通过调控前列腺素在棕色脂肪中的合成，进而影响全身代谢的新机制，拓展了m6A及其他表观遗传修饰在代谢调控中的研究思路。模式图（Credit: Cell Metabolism）参考文献 1 SHAMSI, F.; WANG, C. H.; TSENG, Y. H. The evolving view of thermogenic adipocytes - ontogeny, niche and function. Nat Rev Endocrinol, v. 17, n. 12, p. 726-744, Dec 2021. ISSN 1759-5029 (Print) 1759-5029. 2 CYPESS, A. M. Reassessing Human Adipose Tissue. N Engl J Med, v. 386, n. 8, p. 768-779, Feb 24 2022. ISSN 0028-4793. 3 DE JESUS, D. F. et al. m(6)A mRNA Methylation Regulates Human β-Cell Biology in Physiological States and in Type 2 Diabetes. In: (Ed.). Nat Metab. Germany, v.1, 2019. p.765-774. ISBN 2522-5812 (Electronic) 2522-5812 (Linking). 4 D, F. D. J. et al. Redox regulation of m(6)A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes. Nat Cell Biol, v. 26, n. 3, p. 421-437, Mar 2024. ISSN 1465-7392. 5 KAHRAMAN, S. et al. m6A mRNA Methylation Regulates Early Pancreatic β-Cell Differentiation. bioRxiv, p. 2023.08.03.551675, 2023. Disponível em: < https://www.biorxiv.org/content/biorxiv/early/2023/08/03/2023.08.03.551675.full.pdf >. https://doi.org/10.1016/j.cmet.2024.08.006 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

信使RNA

2024-07-31

·生物探索

Cell Metab | 王童童等发现一种新的脂肪细胞亚群可通过ATP依赖的无效循环来产热

引言在人体维持能量平衡和体温调节的过程中，脂肪组织扮演着至关重要的角色。长期以来，科学家们认为棕色和米色脂肪细胞主要通过解偶联蛋白1 (UCP1) 介导的产热机制来调节能量平衡。然而，近年来的研究表明，可能存在UCP1独立的,依赖ATP无效循环产热机制。这一发现尤其引起了研究者们的兴趣，因为人类的UCP1表达水平普遍较低且个体间差异显著。这种情况促使科学家们探索是否存在其他类型的产热细胞，以及它们如何在人体能量代谢中发挥作用。 2024年7月30日，瑞士苏黎世联邦理工学院的Christian Wolfrum实验室在Cell Metabolism上发表了文章Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle beige cells。他们利用先进的单核RNA测序技术，对小鼠和人类的皮下脂肪组织进行了深入分析。研究团队在小鼠皮下脂肪组织中发现了一种新的产热脂肪细胞亚群，并将其命名为P2细胞。这些P2细胞具有独特的基因表达谱，富含ATP合成酶和氧化磷酸化相关基因，但UCP1的表达水平较低。研究人员发现这些细胞通过ATP依赖的无效循环来产热，而不是依赖传统的UCP1介导的解偶联产热机制。为了进一步验证P2细胞在产热中的作用，研究团队进行了一系列实验。他们发现，当在小鼠体内选择性地消除P2细胞时，这些小鼠的能量消耗显著降低，且在寒冷环境中维持体温的能力明显下降。这一发现强有力地证明了P2细胞在能量代谢中的重要作用。特别值得注意的是，即使在UCP1基因敲除的小鼠中，P2细胞仍然能够发挥其产热功能，这为解释UCP1缺失小鼠仍能适应寒冷环境提供了新的解释。在人类深颈部脂肪组织中，研究者们发现了一种与小鼠P2细胞相似的细胞亚群，被命名为H-Ad-3。团队发现H-Ad-3细胞的丰度与个体在寒冷环境下的产热能力呈正相关。这一发现揭示了H-Ad-3细胞可能是人类适应寒冷环境的重要组成部分。更进一步，研究人员分析了超过1000名参与者的皮下脂肪组织样本，发现H-Ad-3细胞的比例与多项重要的代谢健康指标（如体质指数、空腹血糖、糖化血红蛋白水平等）呈负相关，暗示这些细胞可能在人体整体代谢健康中扮演着重要角色。模式图（Credit: Cell Metabolism）在同期，哈佛大学医学院Dana-Farber癌症研究所的Bruce Spiegelman团队发表了背靠背文章Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle，报道了类似的机制。他们通过开发新的功能性米色脂肪细胞系,并结合单细胞克隆分析，发现了一种独特的脂肪细胞亚群。这些细胞高表达组织非特异性碱性磷酸酶 (TNAP)，但UCP1表达较低。进一步研究表明，这些细胞主要通过ATP依赖的肌酸无效循环产热，而不是经典的UCP1介导的解偶联产热。模式图（Credit: Cell Metabolism）这项研究拓展了我们对能量代谢调控的认识。同时，这一发现为长期困扰科学家的问题——为什么UCP1缺失的小鼠和UCP1表达低的人类仍能进行有效的产热——提供了合理解释。此外，P2/H-Ad-3细胞的发现为开发针对肥胖和代谢疾病的新疗法提供了潜在的靶点。这项研究也强调了脂肪组织异质性在能量代谢中的重要性，提示我们需要更全面地考虑脂肪组织的多样性功能。参考文献 https://doi.org/10.1016/j.cmet.2024.07.005 https://doi.org/10.1016/j.cmet.2024.07.002 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述