由于锚蛋白-B 缺乏导致细胞表面 GLUT4 增加引起的细胞自主肥胖。
Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency.
机构信息
Howard Hughes Medical Institute, Duke University, Durham, NC 27710;
Department of Biochemistry, Duke University, Durham, NC 27710.
出版信息
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):12743-12748. doi: 10.1073/pnas.1708865114. Epub 2017 Nov 13.
Abstract
Obesity typically is linked to caloric imbalance as a result of overnutrition. Here we propose a cell-autonomous mechanism for adiposity as a result of persistent cell surface glucose transporter type 4 (GLUT4) in adipocytes resulting from impaired function of ankyrin-B (AnkB) in coupling GLUT4 to clathrin-mediated endocytosis. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet (HFD). AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4. AnkB binds directly to GLUT4 and clathrin and promotes their association in adipocytes. AnkB variants that fail to restore normal lipid accumulation and GLUT4 localization in adipocytes are present in 1.3% of European Americans and 8.4% of African Americans, and are candidates to contribute to obesity susceptibility in humans.
摘要
肥胖通常与营养过剩导致的热量失衡有关。在这里，我们提出了一种脂肪堆积的细胞自主机制，其原因是脂肪细胞表面葡萄糖转运蛋白 4（GLUT4）持续存在，这是由于锚蛋白-B（AnkB）的功能障碍，导致 GLUT4与网格蛋白介导的内吞作用偶联受损。脂肪组织特异性 AnkB-KO 小鼠随着年龄的增长或高脂肪饮食（HFD）的摄入会发展为肥胖和进行性胰岛功能障碍。AnkB 缺陷型脂肪细胞表现出与葡萄糖摄取增加和 GLUT4 内吞作用受损相关的脂质积累增加。AnkB 直接与 GLUT4 和网格蛋白结合，并促进它们在脂肪细胞中的结合。在 1.3%的欧洲裔美国人和 8.4%的非裔美国人中存在不能恢复脂肪细胞中正常脂质积累和 GLUT4 定位的 AnkB 变体，它们可能是导致人类肥胖易感性的候选因素。
相似文献
1
Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency.由于锚蛋白-B 缺乏导致细胞表面 GLUT4 增加引起的细胞自主肥胖。
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):12743-12748. doi: 10.1073/pnas.1708865114. Epub 2017 Nov 13.
2
Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency.锚蛋白B代谢综合征将年龄依赖性肥胖与胰腺β细胞功能不全结合在一起。
J Clin Invest. 2015 Aug 3;125(8):3087-102. doi: 10.1172/JCI81317. Epub 2015 Jul 13.
3
PID1 regulates insulin-dependent glucose uptake by controlling intracellular sorting of GLUT4-storage vesicles.PID1 通过控制 GLUT4 储存囊泡的细胞内分拣来调节胰岛素依赖的葡萄糖摄取。
Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1592-1603. doi: 10.1016/j.bbadis.2019.03.010. Epub 2019 Mar 21.
4
LMO3 reprograms visceral adipocyte metabolism during obesity.LMO3 重编程肥胖过程中内脏脂肪细胞的代谢。
J Mol Med (Berl). 2021 Aug;99(8):1151-1171. doi: 10.1007/s00109-021-02089-9. Epub 2021 May 20.
5
SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis.SWELL1是脂肪细胞大小、胰岛素信号传导和葡萄糖稳态的调节因子。
Nat Cell Biol. 2017 May;19(5):504-517. doi: 10.1038/ncb3514. Epub 2017 Apr 24.
6
High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance.由脂肪特异性启动子驱动的葡萄糖转运蛋白4的高水平过表达在高脂饮食的转基因小鼠中得以维持，但并不能预防糖耐量受损。
Endocrinology. 1995 Mar;136(3):995-1002. doi: 10.1210/endo.136.3.7867610.
7
Treatment with celastrol protects against obesity through suppression of galanin-induced fat intake and activation of PGC-1α/GLUT4 axis-mediated glucose consumption.用雷公藤红素治疗可通过抑制甘丙肽诱导的脂肪摄入和激活 PGC-1α/GLUT4 轴介导的葡萄糖消耗来预防肥胖。
Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1341-1350. doi: 10.1016/j.bbadis.2019.02.002. Epub 2019 Feb 10.
8
Class II histone deacetylases downregulate GLUT4 transcription in response to increased cAMP signaling in cultured adipocytes and fasting mice.在培养的脂肪细胞和禁食的小鼠中，II 类组蛋白去乙酰化酶响应 cAMP 信号的增加而下调 GLUT4 转录。
Diabetes. 2012 Jun;61(6):1404-14. doi: 10.2337/db11-0737. Epub 2012 Mar 8.
9
Kinin B1 receptor in adipocytes regulates glucose tolerance and predisposition to obesity.脂肪细胞中的激肽 B1 受体调节葡萄糖耐量和肥胖易感性。
PLoS One. 2012;7(9):e44782. doi: 10.1371/journal.pone.0044782. Epub 2012 Sep 14.
10
Effect of Baicalein on GLUT4 Translocation in Adipocytes of Diet-Induced Obese Mice.黄芩苷对饮食诱导肥胖小鼠脂肪细胞中葡萄糖转运蛋白4转位的影响
Cell Physiol Biochem. 2018;50(2):426-436. doi: 10.1159/000494154. Epub 2018 Oct 11.
引用本文的文献
1
Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity.锚蛋白B调节骨骼肌中的线粒体分裂，是最佳耐力运动能力所必需的。
Nat Commun. 2025 Aug 25;16(1):7671. doi: 10.1038/s41467-025-62977-3.
2
TBC1D30 regulates proinsulin and insulin secretion and is the target of a genomic association signal for proinsulin.TBC1D30调节胰岛素原和胰岛素分泌，并且是胰岛素原基因组关联信号的靶点。
Diabetologia. 2025 Jun;68(6):1169-1183. doi: 10.1007/s00125-025-06391-w. Epub 2025 Mar 10.
3
Exploring protein relative relations in skeletal muscle proteomic analysis for insights into insulin resistance and type 2 diabetes.探讨骨骼肌蛋白质组学分析中蛋白质的相对关系，以深入了解胰岛素抵抗和 2 型糖尿病。
Sci Rep. 2024 Jul 31;14(1):17631. doi: 10.1038/s41598-024-68568-4.
4
Young SINEs in pig genomes impact gene regulation, genetic diversity, and complex traits.猪基因组中的年轻 SINEs 影响基因调控、遗传多样性和复杂性状。
Commun Biol. 2023 Aug 31;6(1):894. doi: 10.1038/s42003-023-05234-x.
5
Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle.TUG 蛋白的泛素化处理作为调节脂肪和肌肉葡萄糖摄取和能量代谢的一种机制。
Front Endocrinol (Lausanne). 2022 Sep 29;13:1019405. doi: 10.3389/fendo.2022.1019405. eCollection 2022.
6
Mechanisms underlying the role of ankyrin-B in cardiac and neurological health and disease.锚蛋白B在心脏和神经健康与疾病中作用的潜在机制。
Front Cardiovasc Med. 2022 Aug 4;9:964675. doi: 10.3389/fcvm.2022.964675. eCollection 2022.
7
The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development.免疫检查点B7-H3（CD276）调节脂肪细胞祖细胞代谢和肥胖症发展。
Sci Adv. 2022 Apr 29;8(17):eabm7012. doi: 10.1126/sciadv.abm7012. Epub 2022 Apr 27.
8
Predicts Dual-Drug Resistance to Temozolomide and Bevacizumab in Glioma.预测胶质瘤对替莫唑胺和贝伐单抗的双重耐药性。
Front Oncol. 2021 Dec 17;11:769592. doi: 10.3389/fonc.2021.769592. eCollection 2021.
9
Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A.巨轴索锚蛋白-B 介导轴突导向和侧支分支修剪因子 Sema3A 的转导。
Elife. 2021 Nov 23;10:e69815. doi: 10.7554/eLife.69815.
10
Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.致病性 SPTBN1 变异导致常染色体显性神经发育综合征。
Nat Genet. 2021 Jul;53(7):1006-1021. doi: 10.1038/s41588-021-00886-z. Epub 2021 Jul 1.
本文引用的文献
1
A novel method for the quantification of fatty infiltration in skeletal muscle.一种用于定量骨骼肌脂肪浸润的新方法。
Skelet Muscle. 2017 Jan 10;7(1):1. doi: 10.1186/s13395-016-0118-2.
2
Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes.锚蛋白B是一种PI3P效应蛋白，它通过将RabGAP1L招募到早期内体来促进极化的α5β1整合素循环利用。
Elife. 2016 Oct 8;5:e20417. doi: 10.7554/eLife.20417.
3
An Adaptable Spectrin/Ankyrin-Based Mechanism for Long-Range Organization of Plasma Membranes in Vertebrate Tissues.一种基于血影蛋白/锚蛋白的适应性机制，用于脊椎动物组织中质膜的长距离组织。
Curr Top Membr. 2016;77:143-84. doi: 10.1016/bs.ctm.2015.10.001. Epub 2015 Nov 30.
4
The Genetics of Pediatric Obesity.小儿肥胖症的遗传学
Trends Endocrinol Metab. 2015 Dec;26(12):711-721. doi: 10.1016/j.tem.2015.08.008. Epub 2015 Oct 1.
5
Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency.锚蛋白B代谢综合征将年龄依赖性肥胖与胰腺β细胞功能不全结合在一起。
J Clin Invest. 2015 Aug 3;125(8):3087-102. doi: 10.1172/JCI81317. Epub 2015 Jul 13.
6
Genetic studies of body mass index yield new insights for obesity biology.遗传研究体重指数为肥胖生物学提供了新的见解。
Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.
7
Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia.βII血影蛋白依赖性细胞骨架功能障碍是人类心律失常的基础。
Circulation. 2015 Feb 24;131(8):695-708. doi: 10.1161/CIRCULATIONAHA.114.013708. Epub 2015 Jan 28.
8
A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.一条PIK3C3-锚蛋白B-动力蛋白激活蛋白途径促进轴突生长和多细胞器运输。
J Cell Biol. 2014 Dec 22;207(6):735-52. doi: 10.1083/jcb.201407063.
9
Pancreatic β-cell proliferation in obesity.肥胖状态下胰腺β细胞的增殖
Adv Nutr. 2014 May 14;5(3):278-88. doi: 10.3945/an.113.005488. Print 2014 May.
10
The origins and drivers of insulin resistance.胰岛素抵抗的起源和驱动因素。
Cell. 2013 Feb 14;152(4):673-84. doi: 10.1016/j.cell.2013.01.041.
Zotero 插件