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Mfn1而非Mfn2的缺失会增强脂肪生成。

Loss of Mfn1 but not Mfn2 enhances adipogenesis.

作者信息

Mann Jake P, Tábara Luis Carlos, Patel Satish, Pushpa Pushpa, Alvarez-Guaita Anna, Dong Liang, Haider Afreen, Lim Koini, Tandon Panna, Scurria Fabio, Minchin James E N, O'Rahilly S Stephen, Fazakerley Daniel J, Prudent Julien, Semple Robert K, Savage David B

机构信息

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.

MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom.

出版信息

PLoS One. 2024 Dec 31;19(12):e0306243. doi: 10.1371/journal.pone.0306243. eCollection 2024.

DOI:10.1371/journal.pone.0306243
PMID:39739772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11687706/
Abstract

OBJECTIVE

A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.

METHODS

We characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.

RESULTS

Mfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation. Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers. Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.

CONCLUSIONS

Loss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation.

摘要

目的

线粒体融合蛋白2（MFN2）的双等位基因错义突变可导致多发性对称性脂肪瘤病和部分脂肪营养不良，这表明线粒体融合功能的破坏或其与其他细胞器在脂肪细胞分化、生长和/或存活过程中的相互作用出现异常。在本研究中，我们旨在记录线粒体融合蛋白1（Mfn1）或2（Mfn2）缺失对培养细胞中脂肪生成的影响。

方法

我们对野生型（WT）、Mfn1基因敲除和Mfn2基因敲除的小鼠胚胎成纤维细胞（MEF）以及使用小干扰RNA（siRNA）降低Mfn1或Mfn2水平的3T3-L1前脂肪细胞的脂肪细胞分化情况进行了表征。

结果

Mfn1基因敲除的MEF显示出线粒体网络的显著碎片化，令人惊讶的是，通过脂质积累、脂肪细胞标志物（Plin1、Fabp4、Glut4、Adipoq）的表达以及胰岛素刺激的葡萄糖摄取评估，其分化为脂肪细胞的倾向增强。RNA测序揭示了相应的促脂肪生成转录谱，包括过氧化物酶体增殖物激活受体γ（Pparg）上调。Mfn2基因敲除的MEF也具有破坏的线粒体形态，但与Mfn1基因敲除的MEF相反，它们显示出脂肪细胞标志物的表达降低。在3T3-L1脂肪细胞中进行的Mfn1和Mfn2 siRNA介导的敲低研究通常重复了这些发现。

结论

在培养的前脂肪细胞模型中，Mfn1而非Mfn2的缺失具有促脂肪生成作用。这表明两种线粒体融合蛋白同源物在脂肪细胞分化中具有不同的、非冗余的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/81f429890efd/pone.0306243.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/8716e3eedb03/pone.0306243.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/c3599f1081e9/pone.0306243.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/f073367b9dd7/pone.0306243.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/a7f8c1e67dcf/pone.0306243.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/81f429890efd/pone.0306243.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/8716e3eedb03/pone.0306243.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/c3599f1081e9/pone.0306243.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/f073367b9dd7/pone.0306243.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/a7f8c1e67dcf/pone.0306243.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa48/11687706/81f429890efd/pone.0306243.g005.jpg

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本文引用的文献

1
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Diabetes. 2022 Dec 1;71(12):2572-2583. doi: 10.2337/db22-0450.
2
Gene Set Knowledge Discovery with Enrichr.基因集知识发现与 Enrichr
Curr Protoc. 2021 Mar;1(3):e90. doi: 10.1002/cpz1.90.
3
Twelve years of SAMtools and BCFtools.SAMtools 和 BCFtools 十二年。
Gigascience. 2021 Feb 16;10(2). doi: 10.1093/gigascience/giab008.
4
Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.Charcot-Marie-Tooth 病 2A 型的自然病史：一项大型国际多中心研究。
Brain. 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323.
5
Mitofusin 2 in Macrophages Links Mitochondrial ROS Production, Cytokine Release, Phagocytosis, Autophagy, and Bactericidal Activity.巨噬细胞中的线粒体融合蛋白 2 与线粒体 ROS 产生、细胞因子释放、吞噬作用、自噬和杀菌活性有关。
Cell Rep. 2020 Aug 25;32(8):108079. doi: 10.1016/j.celrep.2020.108079.
6
The mutational constraint spectrum quantified from variation in 141,456 humans.从 141456 名人类个体的变异中量化的突变约束谱。
Nature. 2020 May;581(7809):434-443. doi: 10.1038/s41586-020-2308-7. Epub 2020 May 27.
7
SuperPlots: Communicating reproducibility and variability in cell biology.超图：展示细胞生物学中的可重复性和可变性。
J Cell Biol. 2020 Jun 1;219(6). doi: 10.1083/jcb.202001064.
8
Golgi-derived PI4P-containing vesicles drive late steps of mitochondrial division.高尔基体内含 PI4P 的囊泡驱动线粒体分裂的后期步骤。
Science. 2020 Mar 20;367(6484):1366-1371. doi: 10.1126/science.aax6089.
9
An adipocyte-specific defect in oxidative phosphorylation increases systemic energy expenditure and protects against diet-induced obesity in mouse models.脂肪细胞中氧化磷酸化的特异性缺陷会增加全身能量消耗，并防止小鼠模型中饮食诱导的肥胖。
Diabetologia. 2020 Apr;63(4):837-852. doi: 10.1007/s00125-019-05082-7. Epub 2020 Jan 10.
10
Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in .神经元 TORC1 通过 AMPK 调节长寿和非自主调节线粒体动力学。
Elife. 2019 Aug 14;8:e49158. doi: 10.7554/eLife.49158.