转录因子EB在调控脂质代谢中的研究进展
作者:
作者单位:

(桂林医学院广西糖尿病重点实验室医学重点实验室,广西桂林市 541199)

作者简介:

李慧娟,硕士研究生,研究方向为脂质代谢紊乱相关疾病,E-mail:1379467166@qq.com。通信作者吕运成,博士,教授,博士研究生导师,研究方向为脂质代谢紊乱及相关疾病/血管衰老致动脉粥样硬化的作用与机制,E-mail:anthony0723@163.com。

基金项目:

国家自然科学基金项目(82160098);广西壮族自治区自然科学基金项目(2019JJA140728)


The research advances of transcription factor EB in the regulation of lipid metabolism
Author:
Affiliation:

Guangxi Key Laboratory of Diabetic System Medicine, Guilin Medical University, Guilin, Guangxi 541199, China)

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    摘要:

    转录因子EB(TFEB)属于小眼畸形相关转录因子(MiTF/TFE)家族,是溶酶体功能和自噬的主要调节因子,其通过调节溶酶体内脂质降解、脂肪酸β氧化以及胞内胆固醇流出等途径在调节脂质代谢过程中发挥重要作用。TFEB主要通过介导自噬以及脂质代谢相关因子的表达抑制非酒精性脂肪性肝病和肥胖症的发生,另外通过抑制巨噬细胞和血管平滑肌细胞内脂质蓄积而抑制泡沫细胞的形成延缓动脉粥样硬化的进展,还可通过促进脂噬降低脂质积累及其诱导的胰岛素抵抗与β细胞衰竭进而缓解糖尿病脂质代谢紊乱。总之,TFEB在脂质代谢过程及脂质代谢紊乱相关疾病中发挥关键作用,并可在临床上作为潜在的干预靶点以纠正体内脂质代谢紊乱。

    Abstract:

    Transcription factor EB (TFEB), which belongs to the microphthalmia/transcription factor E (MiTF/TFE) family, is mainly functioned as regulator involved in regulating lysosomal function and autophagy. It plays an important role in lipid metabolism via modulating lysosomal lipid degradation, mitochondrial β-oxidation of fatty acid, and intracellular cholesterol efflux. TFEB inhibits the development of metabolic associated fatty liver disease (MAFLD) and obesity by regulating the autophagy and the expression of lipid metabolism-related genes. Additionally, it prevents the formation of foam cell from macrophages and vascular smooth muscle cells by restraining lipid accumulation, thereby attenuating the progression of atherosclerosis. TFEB promotes lipophagy to relieve lipid accumulation and lipid accumulation-induced insulin resistance, and β-cell failure, deferring diabetes-related lipid metabolic disorders. In summary, TFEB plays a key role in lipid metabolism and associated lipid disorder diseases, and serves as a potential clinical target to correct lipid dysmetabolism in vivo.

    参考文献
    [1] HU J H, LI S Y, YU L H, et al.TFEB:a double-edged sword for tumor metastasis.J Mol Med (Berl), 3,1(8):917-929.
    [2] 王凤玲, 隋小芳, 索树珍, 等.胆固醇代谢紊乱及其相关疾病的研究进展.中国老年保健医学, 2015(1):13-15.WANG F L, SUI X F, SUO S Z, et al.The progress of genetics of cholesterol metabolism disorder and its related diseases.Chin J Geriatric Care, 2015(1):13-15.
    [3] 杨一茗, 柴嘉音, 王雯.TFEB的翻译后修饰对自噬的调节作用.中国动脉硬化杂志, 4,2(3):185-193.YANG Y M, CHAI J Y, WANG W.Regulation of autophagy by posttranslational modification of TFEB.Chin J Arterioscler, 4,2(3):185-193.
    [4] LI M, WANG Z, WANG P, et al.TFEB:a emerging regulator in lipid homeostasis for atherosclerosis.Front Physiol, 1,2:639920.
    [5] SHAO J, LANG Y, DING M, et al.Transcription factor EB:a promising therapeutic target for ischemic stroke.Curr Neuropharmacol, 4,2(2):170-190.
    [6] PEA-LLOPIS S, VEGA-RUBIN-DE-CELIS S, SCHWARTZ J C, et al.Regulation of TFEB and V-ATPases by mTORC1.EMBO J, 1,0(16):3242-3258.
    [7] NAPOLITANO G, BALLABIO A.TFEB at a glance.J Cell Sci, 6,9(13):2475-2481.
    [8] COUREY A J, HOLTZMAN D A, JACKSON S P, et al.Synergistic activation by the glutamine-rich domains of human transcription factor Sp1.Cell, 9,9(5):827-836.
    [9] FRANCO-JUREZ B, CORONEL-CRUZ C, HERNNDEZ-OCHOA B, et al.TFEB; Beyond its role as an autophagy and lysosomes regulator.Cells, 2,1(19):3153.
    [10] 刘惠美, 彭国龙, 欧阳雪倩, 等.选择性自噬和动脉粥样硬化.中国动脉硬化杂志, 3,1(9):737-5,3.LIU H M, PENG G L, OUYANG X Q, et al.Advances in selective autophagy and atherosclerosis.Chin J Arterioscler, 3,1(9):737-5,3.
    [11] ALIM AL-BARI A, ITO Y, THOMES P G, et al.Emerging mechanistic insights of selective autophagy in hepatic diseases.Front Pharmacol, 3,4:1149809.
    [12] SETTEMBRE C, DE CEGLI R, MANSUETO G, et al.TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop.Nat Cell Biol, 3,5(6):647-658.
    [13] SETTEMBRE C, BALLABIO A.Lysosome:regulator of lipid degradation pathways.Trends Cell Biol, 4,4(12):743-750.
    [14] ZHAO X, XUE X, WANG J, et al.Quercetin alleviates ethanol-induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy.Phytother Res, 3,7(1):62-76.
    [15] MANSUETO G, ARMANI A, VISCOMI C, et al.Transcription factor EB controls metabolic flexibility during exercise.Cell Metab, 7,5(1):182-196.
    [16] LI X, ZHANG X, ZHENG L, et al.Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB.Cell Death Dis, 6,7(12):e2527.
    [17] ROBICHAUD S, FAIRMAN G, VIJITHAKUMAR V, et al.Identification of novel lipid droplet factors that regulate lipophagy and cholesterol efflux in macrophage foam cells.Autophagy, 1,7(11):3671-3689.
    [18] FOUGERAT A, MONTAGNER A, LOISEAU N, et al.Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease.Cells, 0,9(7):1638.
    [19] DU X, DI MALTA C, FANG Z, et al.Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway.Acta Pharm Sin B, 2,2(6):2869-2886.
    [20] GONG Q, ZHANG X, SUN Y, et al.Transcription factor EB inhibits non-alcoholic fatty liver disease through fibroblast growth factor 21.J Mol Med (Berl), 2,0(11):1587-1597.
    [21] REN Q, SUN Q, FU J.Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.Autophagy, 4,0(2):221-241.
    [22] WANG Y, GUNEWARDENA S, LI F, et al.An FGF15/19-TFEB regulatory loop controls hepatic cholesterol and bile acid homeostasis.Nat Commun, 0,1(1):3612.
    [23] PI H, WANG Z, LIU M, et al.SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL-treated human vascular smooth muscle cells.J Cell Mol Med, 9,3(8):5259-5269.
    [24] CHEN Z, OUYANG C, ZHANG H, et al.Vascular smooth muscle cell-derived hydrogen sulfide promotes atherosclerotic plaque stability via TFEB (transcription factor EB)-mediated autophagy.Autophagy, 2,8(10):2270-2287.
    [25] OUIMET M, MARCEL Y L.Regulation of lipid droplet cholesterol efflux from macrophage foam cells.Arterioscler Thromb Vasc Biol, 2,2(3):575-581.
    [26] LI X, ZHU R, JIANG H, et al.Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis.Acta Pharm Sin B, 2,2(5):2280-2299.
    [27] EMANUEL R, SERGIN I, BHATTACHARYA S, et al.Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid-induced lysosomal dysfunction and downstream sequelae.Arterioscler Thromb Vasc Biol, 4,4(9):1942-1952.
    [28] GABRIEL T L, TOL M J, OTTENHOF R, et al.Lysosomal stress in obese adipose tissue macrophages contributes to MITF-dependent Gpnmbinduction.Diabetes, 4,3(10):3310-3323.
    [29] LIU L, TAO Z, ZHENG L D, et al.FoxO1 interacts with transcription factor EB and differentially regulates mitochondrial uncoupling proteins via autophagy in adipocytes.Cell Death Discov, 6,2:16066.
    [30] ZHOU J, LU Y, LIN Y, et al.Overexpression of hepatic pescadillo 1 in obesity induces lipid dysregulation by inhibiting autophagy.Transl Res, 3,8:1-15.
    [31] KIM J, KIM S H, KANG H, et al.TFEB-GDF15 axis protects against obesity and insulin resistance as a lysosomal stress response.Nat Metab, 1,3(3):410-427.
    [32] PASTORE N, VAINSHTEIN A, KLISCH T J, et al.TFE3 regulates whole-body energy metabolism in cooperation with TFEB.EMBO Mol Med, 7,9(5):605-621.
    [33] JI J, PETROPAVLOVSKAIA M, KHATCHADOURIAN A, et al.Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells.J Cell Mol Med, 9,3(4):2890-2900.
    [34] LIM H, LIM Y M, KIM K H, et al.A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes.Nat Commun, 8,9(1):1438.
    [35] TRIVEDI P C, BARTLETT J J, PEREZ L J, et al.Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes.Biochim Biophys Acta, 6,1(12 Pt A):1893-1910.
    [36] SALMA N, SONG J S, KAWAKAMI A, et al.Tfe3 and Tfeb transcriptionally regulate peroxisome proliferator-activated receptor γ2 expression in adipocytes and mediate adiponectin and glucose levels in mice.Mol Cell Biol, 7,7(15):e00608-e00616.
    [37] SCHILLING J D, MACHKOVECH H M, HE L, et al.TLR4 activation under lipotoxic conditions leads to synergistic macrophage cell death through a TRIF-dependent pathway.J Immunol, 3,0(3):1285-1296.
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李慧娟,王云,邝彤东,吕运成.转录因子EB在调控脂质代谢中的研究进展[J].中国动脉硬化杂志,2025,33(5):378~384, 394.

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  • 收稿日期:2024-04-30
  • 最后修改日期:2024-06-14
  • 在线发布日期: 2025-06-03