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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (6): 63-73    DOI: 10.13523/j.cb.2001041
综述     
自噬调控白色脂肪细胞棕色化的研究进展 *
曾祥意,潘杰()
山东师范大学生命科学学院 济南 250014
Progress on Autophagy Regulation of Browning of White Adipose Cells
ZENG Xiang-Yi,PAN Jie()
College of Life Sciences, Shandong Normal University, Jinan 250014, China
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摘要：

脂肪细胞自噬(autophagy)以脂自噬和线粒体自噬的形式存在。细胞通过脂自噬调节脂质代谢,降低脂毒性并为线粒体活动提供原料;通过线粒体自噬控制细胞数量和质量影响细胞的功能。白色脂肪细胞中脂质过度积累及自噬调控异常引起的炎症,可导致肥胖症及其相关代谢疾病的发生。通过白色脂肪细胞棕色化将储能的白色脂肪细胞转变成产热的米色脂肪细胞是防治肥胖症的策略之一,而白色脂肪细胞棕色化过程需要自噬的调控。就目前有关两种形式的自噬在白色脂肪细胞棕色化中的作用、相关信号通路及自噬调节炎症的研究进展做一综述评论,以期为抗肥胖及其相关代谢性疾病研究提供参考依据。
关键词： 自噬;  白色脂肪细胞棕色化;  肥胖;  炎症    
Abstract:

Autophagy of adipocytes is mainly in the form of Lipophagy and Mitophagy. Lipophagy reduces lipotoxicity of adipocytes and provides substrate for mitochondria by promoting lipolysis. Mitophagy controls the quantity and quality of mitochondria to affect the function of the cells. Excessive accumulation of white adipose tissues and inflammation caused by inappropriate autophagy regulation can lead to obesity and its related metabolic diseases. The conversion of stored white adipose cells into heat-producing beige cells by browning of white adipocytes is one of the current strategies to prevent obesity. The process of browning of white adipose cells is inseparable from the regulation of autophagy. This article reviews the current research progress on the role of two forms of autophagy in browning of white adipose cells, related signaling pathways, and autophagy-regulated inflammation, with a view to providing reference for the study of anti-obesity and related metabolic diseases.
Key words: Autophagy    White adipose cells browning    Obesity    Inflammation
收稿日期: 2020-01-14 出版日期: 2020-06-23
ZTFLH:  Q291  
基金资助: * 国家自然科学基金(81070685);山东省自然科学基金(ZR2018MC013)
通讯作者: 潘杰     E-mail: jiepan@sdnu.edu.cn
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曾祥意,潘杰. 自噬调控白色脂肪细胞棕色化的研究进展 *[J]. 中国生物工程杂志, 2020, 40(6): 63-73.

ZENG Xiang-Yi,PAN Jie. Progress on Autophagy Regulation of Browning of White Adipose Cells. China Biotechnology, 2020, 40(6): 63-73.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2001041    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I6/63

图1  脂肪细胞自噬机制
图2  自噬通过PI3K-AKT-mTOR信号通路参与调控白色脂肪细胞棕色化
图3  自噬调控白色脂肪细胞棕色化AMPK-SIRT1信号通路
图4  自噬调控白色脂肪细胞棕色化cAMP-PKA-CREBP信号通路
[1] Hansard S L . Residual organ blood volume of cattle, sheep and swine. Proc Soc Exp Biol Med, 1956,91(1):31.
pmid: 13297700
[2] Duve C D . Structure and functions of lysosomes. Funktionelle und Morphologische Organisation der Zelle, 1963, 209-218.
[3] Tsukada M, Ohsumi Y . Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. Febs Letters, 1993,333(4):169-174.
[4] Mizushima N, Noda T, Yoshimori T , et al. A protein conjugation system essential for autophagy. Nature, 1998,395(6700):395-398.
[5] Liu Y, Levine B . Autosis and autophagic cell death: the dark side of autophagy. Cell Death & Differentiation, 2015,22(3):367-376.
doi: 10.1038/cdd.2014.143 pmid: 25257169
[6] Romero M, Zorzano A . Role of autophagy in the regulation of adipose tissue biology. Cell Cycle, 2019,18(13):1435-1445.
doi: 10.1080/15384101.2019.1624110 pmid: 31135269
[7] Kajimura S, Saito M . A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol, 2014,76(1):225-249.
[8] Ricquier D . Uncoupling protein 1 of brown adipocytes, the only uncoupler: Aahistorical perspective. Front Endocrinol (Lausanne), 2011,2:85.
[9] Cinti S . Transdifferentiation properties of adipocytes in the adipose organ. Am J Physiol Endocrinol Metab, 2009,297(5):977-986.
[10] Wu J, Boström P, Sparks L M , et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 2012,150(2):366-376.
[11] Asano H, Kanamori Y, Higurashi S , et al. Induction of beige-like adipocytes in 3T3-L1 cells. J Vet Med Sci, 2014,76(1):57-64.
doi: 10.1292/jvms.13-0359 pmid: 24065084
[12] Sanchez-Gurmaches J, Hung C M, Sparks C A , et al. PTEN loss in the myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from myf5 precursors. Cell Metabolism, 2012,16(3):348-362.
[13] Fan L, Xu H, Yang R , et al. Combination of capsaicin and capsiate induces browning in 3T3-L1 white adipocytes via activation of the peroxisome proliferator-activated receptor γ/β3-adrenergic receptor signaling pathways. J Agric Food Chem, 2019,67(22):6232-6240.
[14] Lee J M, Wagner M, Xiao R , et al. Nutrient-sensing nuclear receptors coordinate autophagy. Nature, 2014,516(7529):112-115.
pmid: 25383539
[15] Lu Y, Fujioka H, Joshi D , et al. Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge. Sci Rep, 2018,8(1):8251.
[16] Qian M, Fang X, Wang X . Autophagy and inflammation. Clin Transl Med, 2017,6(1):24.
[17] Mrschtik M, Ryan K M . Lysosomal proteins in cell death and autophagy. Febs J, 2015,282(10):1858-1870.
doi: 10.1111/febs.13253 pmid: 25735653
[18] Namkoong S, Lee K I, Lee J I , et al. The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase. Autophagy, 2015,11(5):756-68.
[19] Ferhat M, Funai K, Boudina S . Autophagy in adipose tissue physiology and pathophysiology. Antioxid Redox Signal, 2019,31(6):487-501.
[20] Itakura E, Kishi-Itakura C, Koyama-Honda I , et al. Structures containing Atg9A and the ULK1 complex independently target depolarized mitochondria at initial stages of Parkin-mediated mitophagy. J Cell Sci, 2012,125(Pt 6):1488-1499.
[21] Jansen H J, van Essen P, Koenen T , et al. Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology, 2012,153(12):5866-5874.
doi: 10.1210/en.2012-1625 pmid: 23117929
[22] Kabeya Y, Mizushima N, Ueno T , et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J, 2000,19(21):5720-5728.
doi: 10.1093/emboj/19.21.5720 pmid: 11060023
[23] Liu H Y, Han J, Cao S Y , et al. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem, 2009,284(45):31484-31492.
[24] Wang H, Sun H Q, Zhu X , et al. GABARAPs regulate PI4P-dependent autophagosome: lysosome fusion. Proc Natl Acad Sci U S A, 2015,112(22):7015-7020.
[25] Perera R M, Stoykova S, Nicolay B N , et al. Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature, 2015,524(7565):361-365.
[26] Hamasaki M, Furuta N, Matsuda A , et al. Autophagosomes form at ER-mitochondria contact sites. Nature, 2013,495(7441):389-393.
doi: 10.1038/nature11910 pmid: 23455425
[27] Parzych K R, Klionsky D J . An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal, 2013,20(3):460-473.
doi: 10.1089/ars.2013.5371 pmid: 23725295
[28] Roa-Mansergas X, Fadó R, Atari M , et al. CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy. Sci Rep, 2018,8(1):6997.
[29] Pickles S, Vigié P, Youle R J . Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol, 2018,28(4):R170-R185.
[30] Schaffer J E . Lipotoxicity: when tissues overeat. Curr Opin Lipidol, 2003,14(3):281-287.
doi: 10.1097/00041433-200306000-00008 pmid: 12840659
[31] Henne W M, Reese M L, Goodman J M . The assembly of lipid droplets and their roles in challenged cells. EMBO J, 2019,38(9).
pmid: 30804003
[32] Kaur J, Debnath J . Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol, 2015,16(8):461-472.
pmid: 26177004
[33] Schott M B, Weller S G, Schulze R J . Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes. J Cell Biol, 2019,218(10):3320-3335.
doi: 10.1083/jcb.201803153 pmid: 31391210
[34] Martinez-Lopez N, Garcia-Macia M, Sahu S , et al. Autophagy in the CNS and periphery coordinate lipophagy and lipolysis in the brown adipose tissue and liver. Cell Metab, 2016,23(1):113-27.
[35] Rambold A S, Cohen S, Lippincott-Schwartz J . Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev Cell, 2015,32(6):678-692.
[36] Singh R, Kaushik S, Wang Y , et al. Autophagy regulates lipid metabolism. Nature, 2009,458(6):1131-1135.
[37] Alexaki A, Gupta S D, Majumder S , et al. Autophagy regulates sphingolipid levels in the liver. J Lipid Res, 2014,55(12).
[38] Li Z, Weller S G, Drizyte-Miller K , et al. Maturation of lipophagic organelles in hepatocytes is dependent upon a rab10-dynamin-2 complex. Hepatology, 2019.
doi: 10.1002/hep.31407 pmid: 32500593
[39] Sathyanarayan A, Mashek M T, Mashek D G . ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism. Cell Rep, 2017,19(1):1-9.
pmid: 28380348
[40] Liu K, Czaja M J . Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ, 2013,20(1):3-11.
[41] Tian Y, Yang B, Qiu W , et al. ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy. Nat Commun, 2019,10(1):3391.
pmid: 31358770
[42] Zhang Y, Goldman S, Baerga R , et al. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci U S A, 2009,106(47):19860-19865.
[43] Singh R, Xiang Y Q, Wang Y J , et al. Autophagy regulates adipose mass and differentiation in mice. J Clin Invest, 2009,119(11):3329-3339.
pmid: 19855132
[44] Rodriguez A, Durán A, Selloum M , et al. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab, 2006,3(3):211-222.
pmid: 16517408
[45] Rocchi A, He C . Emerging roles of autophagy in metabolism and metabolic disorders. Front Biol (Beijing), 2015,10(2):154-164.
[46] Litwinoff E M S, Gold M Y, Singh K , et al. Myeloid ATG16L1 does not affect adipose tissue inflammation or body mass in mice fed high fat diet. Obes Res Clin Pract, 2018,12(2):174-186.
doi: 10.1016/j.orcp.2017.10.006 pmid: 29103907
[47] Kang Y H, Cho M H, Kim J Y , et al. Impaired macrophage autophagy induces systemic insulin resistance in obesity. Oncotarget, 2016,7(24):35577-35591.
[48] Canadas-Lozano D, Marin-Aguilar F, Castejon-Vega B , et al. Blockade of the NLRP3 inflammasome improves metabolic health and lifespan in obese mice. Geroscience, 2020.
pmid: 32363429
[49] Lazarou M, Sliter D A, Kane L A , et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature, 2015,524(7565):309-314.
[50] Zhang Y, Yao Y, Qiu X , et al. Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing. Nat Immunol, 2019,20(4):433-446.
[51] Morishita H, Eguchi S, Kimura H , et al. Deletion of autophagy-related 5 (Atg5) and Pik3c3 genes in the lens causes cataract independent of programmed organelle degradation. J Biol Chem, 2013,288(16):11436-11447.
doi: 10.1074/jbc.M112.437103 pmid: 23479732
[52] Zhang Y, Liu Q, Li Y , et al. PTEN-induced putative kinase 1 (PINK1)/parkin-mediated mitophagy protects PC12 cells against cisplatin-induced neurotoxicity. Med Sci Monit, 2019,25:8797-8806.
[53] Wei Y, Chiang W C, Sumpter R Jr , et al. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell, 2017,168(1-2):224-238.
[54] Yan C, Gong L, Chen L , et al. PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis. Autophagy, 2019,16:1-16.
pmid: 31516068
[55] Kelly D P, Scarpulla R C . Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev, 2004,18(4):357-368.
doi: 10.1101/gad.1177604 pmid: 15004004
[56] Lu X, Altshuler-Keylin S . Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism. Sci Signal, 2018,11(527).
[57] Taylor D, Gottlieb R A . Parkin-mediated mitophagy is downregulated in browning of white adipose tissue. Obesity (Silver Spring), 2017,25(4):704-712.
[58] Kim D, Kim J H . Suppression of brown adipocyte autophagy improves energy metabolism by regulating mitochondrial turnover. Int J Mol Sci, 2019,20(14).
[59] Marques A P, Rosmaninho-Salgado J, Estrada M , et al. Hypoxia mimetic induces lipid accumulation through mitochondrial dysfunction and stimulates autophagy in murine preadipocyte cell line. Biochim Biophys Acta Gen Subj, 2016,1861(3):673-682.
doi: 10.1016/j.bbagen.2016.12.005 pmid: 27939617
[60] Altshuler-Keylin S, Kajimura S . Mitochondrial homeostasis in adipose tissue remodeling. Sci Signal, 2017,10(468).
doi: 10.1126/scisignal.aan0450 pmid: 28246195
[61] Chattopadhyay M, Khemka V K, Chatterjee G , et al. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol Cell Biochem, 2015,399(1-2):95-103.
[62] Wu H, Wang Y, Li W , et al. Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome. Autophagy, 2019,15(11):1882-1898.
doi: 10.1080/15548627.2019.1596482 pmid: 30898010
[63] Lu X . Maintaining mitochondria in beige adipose tissue. Adipocyte, 2019,8(1):77-82.
[64] Sanchez-Gurmaches J, Martinez Calejman C, Jung S M , et al. Brown fat organogenesis and maintenance requires AKT1 and AKT2. Mol Metab, 2019,23:60-74.
pmid: 30833219
[65] Li J, Chen C, Li Y , et al. Inhibition of insulin/PI3K/AKT signaling decreases adipose Sortilin 1 in mice and 3T3-L1 adipocytes. Biochim Biophys Acta Mol Basis Dis, 2017,1863(11):2924-2933.
doi: 10.1016/j.bbadis.2017.08.012 pmid: 28844948
[66] Kajimura S, Seale P, Kubota K , et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature, 2009,460(7259):1154-1158.
[67] Inoki K, Kim J, Guan K L . AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol, 2012,52:381-400.
doi: 10.1146/annurev-pharmtox-010611-134537 pmid: 22017684
[68] Li Y, Yang P, Zhao L , et al. CD36 plays a negative role in the regulation of lipophagy in hepatocytes through an AMPK-dependent pathway. J Lipid Res, 2019,60(4):844-855.
[69] Egan D F, Shackelford D B, Mihaylova M M , et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science, 2011,331(6016):456-461.
[70] Lee I H, Cao L, Mostoslavsky R , et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A, 2008,105(9):3374-3379.
pmid: 18296641
[71] Song Y M, Lee Y H, Kim G W , et al. Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway. Autophagy, 2015,11(1):46-59.
pmid: 25484077
[72] Ou X, Lee M R, Huang X , et al. SIRT1 positively regulates autophagy and mitochondria function in embryonic stem cells under oxidative stress. Stem Cells, 2014,32(5):1183-1194.
doi: 10.1002/stem.1641 pmid: 24449278
[73] Akabane S, Uno M, Tani N , et al. PKA regulates PINK1 stability and parkin recruitment to damaged mitochondria through phosphorylation of MIC60. Mol Cell, 2016,62(3):371-384.
doi: 10.1016/j.molcel.2016.03.037 pmid: 27153535
[74] Subramanian V, Rothenberg A, Gomez C , et al. Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes. J Biol Chem, 2004,279(40):42062-42071.
pmid: 15292255
[75] Lizaso A, Tan K T, Lee Y H . β-adrenergic receptor-stimulated lipolysis requires the RAB7-mediated autolysosomal lipid degradation. Autophagy, 2013,9(8):1228-1243.
doi: 10.4161/auto.24893 pmid: 23708524
[76] Saltiel A R, Kahn C R . Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 2001,414(6865):799-806.
doi: 10.1038/414799a pmid: 11742412
[77] Zang L, Kothan S, Yang Y et al. Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro. Adipocyte, 2020,9(1):24-34.
pmid: 31989870
[78] 黄坤 . 胰岛素信号影响小鼠和人脂肪干细胞棕色化及其机制探讨. 济南:山东师范大学, 2018.
Huang K . Effect of insulin signal on Browning of mouse and human fat stem cells and its mechanism. Jinan: Shandong Normal University, 2018.
[79] 郭聪聪 . 自噬在胰岛素介导的3T3-L1脂肪细胞去分化中的作用机制. 济南:山东师范大学, 2019.
Guo C C . Mechanism of autophagy in insulin-mediated 3T3-L1 adipocyte dedifferentiation. Jinan: Shandong Normal University, 2019.
[80] Takagaki Y, Lee S M, Dongqing Z , et al. Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis. Autophagy, 2020: 1-10.
doi: 10.1080/15548627.2020.1764210 pmid: 32453967
[81] Cao Q, Du H, Fu X , et al. Artemisinin attenuated atherosclerosis in high-fat diet-fed ApoE-/- mice by promoting macrophage autophagy via AMPK/mTOR/ULK1 pathway. J Cardiovasc Pharmacol, 2019.
pmid: 32398478
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