Research Progress on Glycolipid Metabolism Reprogramming of Macrophage in Non-alcoholic Fatty Liver Disease

doi:10.19586/j.2095-2341.2023.0164

Current Biotechnology ›› 2024, Vol. 14 ›› Issue (3): 399-405.DOI: 10.19586/j.2095-2341.2023.0164

• Reviews • Previous Articles Next Articles

Research Progress on Glycolipid Metabolism Reprogramming of Macrophage in Non-alcoholic Fatty Liver Disease

Zhaoqing XI¹^,²^,³(), Mingwei BAO¹^,²^,³()

^1.Department of Cardiology，Renmin Hospital of Wuhan University，Wuhan 430060，China
^2.Cardiovascular Research Institute of Wuhan University，Wuhan 430060，China
^3.Hubei Key Laboratory of Cardiology，Wuhan 430060，China

Received:2023-12-15 Accepted:2024-01-24 Online:2024-05-25 Published:2024-06-18
Contact: Mingwei BAO

巨噬细胞糖脂代谢重编程在非酒精性脂肪肝中的研究进展

席照青¹^,²^,³(), 包明威¹^,²^,³()

^1.武汉大学人民医院心血管内科，武汉 430060
^2.武汉大学心血管病研究所，武汉 430060
^3.心血管病湖北省重点实验室，武汉 430060

通讯作者: 包明威
作者简介:席照青 E-mail: 1067089758@qq.com；
基金资助:
国家自然科学基金项目(81770507)

Abstract

Abstract:

Non-alcoholic fatty liver disease （NAFLD） is the most common chronic liver disease in China， involving various pathophysiological processes such as steatosis， inflammation， and fibrosis. The liver contains a large number of macrophages. More and more evidence suggests that the glycolipid metabolism characteristics of macrophages have changed significantly during the progress of non-alcoholic fatty liver disease， and the regulation of metabolism can regulate the immune function of macrophages， which in turn affects the local inflammatory environment of the liver and the metabolism of hepatocytes. This article reviewed the changes in glycolipid metabolism of macrophages during the progress of NAFLD and the key molecules involved in the above processes， in order to find new targets for the treatment of NAFLD.

Key words: non-alcoholic fatty liver disease, macrophage, glycolipid metabolic reprogramming

摘要：

非酒精性脂肪肝（non-alcoholic fatty liver disease, NAFLD）是我国最常见的慢性肝病，涉及脂肪变性、炎症、纤维化等多种生理病理过程。肝脏中含有大量巨噬细胞，越来越多的证据表明在非酒精性脂肪肝进展过程中巨噬细胞的糖脂代谢特征发生了显著变化，且调控代谢可以调节巨噬细胞的免疫功能，进而影响肝脏局部的炎症环境及肝细胞的代谢。综述了NAFLD的进展过程中巨噬细胞的糖脂代谢的变化以及参与上述过程的关键分子，以期为NAFLD治疗找到新靶点。

关键词: 非酒精性脂肪肝, 巨噬细胞, 糖脂代谢重编程

CLC Number:

Q485

Zhaoqing XI, Mingwei BAO. Research Progress on Glycolipid Metabolism Reprogramming of Macrophage in Non-alcoholic Fatty Liver Disease[J]. Current Biotechnology, 2024, 14(3): 399-405.

席照青, 包明威. 巨噬细胞糖脂代谢重编程在非酒精性脂肪肝中的研究进展[J]. 生物技术进展, 2024, 14(3): 399-405.

References 56

1	HAN S K, BAIK S K, KIM M Y. Non-alcoholic fatty liver disease: definition and subtypes[J]. Clin. Mol. Hepatol., 2023, 29(sl): S5-S16.
2	HAN J, ZHANG X, LAU J K, et al.. Bone marrow-derived macrophage contributes to fibrosing steatohepatitis through activating hepatic stellate cells[J]. J. Pathol., 2019, 248(4): 488-500.
3	BARREBY E, CHEN P, AOUADI M. Macrophage functional diversity in NAFLD—more than inflammation[J]. Nat. Rev. Endocrinol., 2022, 18: 461-472.
4	ZHANG W, LANG R. Macrophage metabolism in nonalcoholic fatty liver disease[J/OL]. Front. Immunol., 2023, 14: 1257596[2024-04-02]. .
5	LIU W, LIU T, ZHENG Y, et al.. Metabolic reprogramming and its regulatory mechanism in sepsis-mediated inflammation[J]. J. Inflamm. Res., 2023, 16: 1195-1207.
6	SUN H J, ZHENG G L, WANG Z C, et al.. Chicoric acid ameliorates sepsis-induced cardiomyopathy via regulating macrophage metabolism reprogramming[J/OL]. Phytomedicine, 2024, 123: 155175[2024-04-02]. .
7	BANG B R, MIKI H, KANG Y J. Mitochondrial PGAM5-Drp1 signaling regulates the metabolic reprogramming of macrophages and regulates the induction of inflammatory responses[J/OL]. Front. Immunol., 2023, 14: 1243548[2024-01-19]. .
8	GUO S, ZHANG C, ZENG H, et al.. Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect[J/OL]. Mol. Metab., 2023, 77: 101796[2024-01-19]. .
9	HU X, WAN X, DIAO Y, et al.. Fibrinogen-like protein 2 regulates macrophage glycolytic reprogramming by directly targeting PKM2 and exacerbates alcoholic liver injury[J/OL]. Int. Immunopharmacol., 2023, 124: 110957[2024-01-19]. .
10	SANG S Y, WANG Y J, LIANG T, et al.. Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice[J/OL]. Int. Immunopharmacol., 2024, 128: 111546[2024-01-19]. .
11	RAO J, WANG H, NI M, et al.. FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2[J]. Gut, 2022, 71(12): 2539-2550.
12	IOVINO M, COLONVAL M, WILKIN C, et al.. Novel XBP1s-independent function of IRE1 RNase in HIF-1α-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid[J/OL]. Front. Immunol., 2023, 14: 1204126[2024-01-19]. .
13	GROEGER M, MATSUO K, HEIDARY ARASH E, et al.. Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages[J/OL]. Nat. Commun., 2023, 14: 3902[2024-01-19]. .
14	LI J, WANG T, XIA J, et al.. Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases[J]. FASEB J., 2019, 33(11): 11640-11654.
15	XU F, GUO M, HUANG W, et al.. Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH[J/OL]. Redox Biol., 2020, 36: 101634[2024-01-19]. .
16	YANG Y, SHENG J, SHENG Y, et al.. Lapachol treats non-alcoholic fatty liver disease by modulating the M1 polarization of Kupffer cells via PKM2[J/OL]. Int. Immunopharmacol., 2023, 120: 110380[2024-01-19]. .
17	FAN N, ZHANG X, ZHAO W, et al.. Covalent inhibition of pyruvate kinase M2 reprograms metabolic and inflammatory pathways in hepatic macrophages against non-alcoholic fatty liver disease[J]. Int. J. Biol. Sci., 2022, 18(14): 5260-5275.
18	INOMATA Y, OH J W, TANIGUCHI K, et al.. Downregulation of miR-122-5p activates glycolysis via PKM2 in kupffer cells of rat and mouse models of non-alcoholic steatohepatitis[J/OL]. Int. J. Mol. Sci., 2022, 23(9): 5230[2024-01-19]. .
19	KONG Q, LI N, CHENG H, et al.. HSPA12A is a novel player in nonalcoholic steatohepatitis via promoting nuclear PKM2-mediated M1 macrophage polarization[J]. Diabetes, 2019, 68(2): 361-376.
20	ISMAIL A, TANASOVA M. Importance of GLUT transporters in disease diagnosis and treatment[J/OL]. Int. J. Mol. Sci., 2022, 23(15): 8698[2024-01-19]. .
21	WAN L, XIA T, DU Y, et al.. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells[J]. FASEB J., 2019, 33(7): 8530-8542.
22	ZHAO H, LU J, HE F, et al.. Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway via IRS2-proteasome degradation[J/OL]. Immunology, 2022, 13: 931087[2024-01-19]. .
23	FREEMERMAN A J, JOHNSON A R, SACKS G N, et al.. Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype[J]. J. Biol. Chem., 2014, 289(11): 7884-7896.
24	WANG X, DE CARVALHO R M, IRACHETA-VELLVE A, et al.. Macrophage-specific hypoxia-inducible factor-1α contributes to impaired autophagic flux in nonalcoholic steatohepatitis[J]. Hepatology, 2019, 69(2): 545-563.
25	CORNWELL A, ZIÓŁKOWSKI H, BADIEI A, et al.. Glucose transporter Glut1-dependent metabolic reprogramming regulates lipopolysaccharide-induced inflammation in RAW264.7 macrophages[J/OL]. Biomolecules, 2023, 13(5): 770[2024-01-19]. .
26	NOE J T, MITCHELL R A. Tricarboxylic acid cycle metabolites in the control of macrophage activation and effector phenotypes[J]. J. Leukoc. Biol., 2019, 106(2): 359-367.
27	RYAN D G, O'NEILL L A J. Krebs cycle reborn in macrophage immunometabolism[J]. Annu. Rev. Immunol., 2020, 38: 289-313.
28	RUSSO S, KWIATKOWSKI M, GOVORUKHINA N, et al.. Meta-inflammation and metabolic reprogramming of macrophages in diabetes and obesity: the importance of metabolites[J/OL]. Front. Immunol., 2021, 12: 746151[2024-01-19]. .
29	XU J, TIAN Z, LI Z, et al.. Puerarin-tanshinone IIA suppresses atherosclerosis inflammatory plaque via targeting succinate/HIF-1α/IL-1β axis[J/OL]. J. Ethnopharmacol., 2023, 317: 116675[2024-01-19]. .
30	VAN DIEPEN J A, ROBBEN J H, HOOIVELD G J, et al.. SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes[J]. Diabetologia, 2017, 60(7): 1304-1313.
31	LIU X J, XIE L, DU K, et al.. Succinate-GPR-91 receptor signalling is responsible for nonalcoholic steatohepatitis-associated fibrosis: effects of DHA supplementation[J]. Liver Int., 2020, 40(4): 830-843.
32	STAŇKOVÁ P, KUČERA O, PETEROVÁ E, et al.. Western diet decreases the liver mitochondrial oxidative flux of succinate: insight from a murine NAFLD model[J/OL]. Int. J. Mol. Sci., 2021, 22(13): 6908[2024-01-19]. .
33	ZHOU Q, WANG Y, LU Z, et al.. Mitochondrial dysfunction caused by SIRT3 inhibition drives proinflammatory macrophage polarization in obesity[J]. Obes. Silver Spring, 2023, 31(4): 1050-1063.
34	LITTLEWOOD-EVANS A, SARRET S, APFEL V, et al.. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis[J]. J. Exp. Med., 2016, 213(9): 1655-1662.
35	KEIRAN N, CEPERUELO-MALLAFRÉ V, CALVO E, et al.. SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity[J]. Nat. Immunol., 2019, 20: 581-592.
36	LEROUX A, FERRERE G, GODIE V, et al.. Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis[J]. J. Hepatol., 2012, 57(1): 141-149.
37	HOEKSTRA M, OUT R, KRUIJT J K, et al.. Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells[J]. J. Hepatol., 2005, 42(3): 400-407.
38	JIN R, HAO J, YI Y, et al.. Regulation of macrophage functions by FABP-mediated inflammatory and metabolic pathways[J/OL]. Biochim. Biophys. Acta Mol. Cell Biol. Lipds., 2021, 1866(8): 158964[2024-01-19]. .
39	LI H, XIAO Y, TANG L, et al.. Adipocyte fatty acid-binding protein promotes palmitate-induced mitochondrial dysfunction and apoptosis in macrophages[J/OL]. Front. Immunol., 2018, 9: 81[2024-01-19]. .
40	ZHANG Y, RAO E, ZENG J, et al.. Adipose fatty acid binding protein promotes saturated fatty acid-induced macrophage cell death through enhancing ceramide production[J]. J. Immunol., 2017, 198(2): 798-807.
41	HOO R L, LEE I P, ZHOU M, et al.. Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice[J]. J. Hepatol., 2013, 58(2): 358-364.
42	O'REILLY M E, KAJANI S, RALSTON J C, et al.. Nutritionally derived metabolic cues typical of the obese microenvironment increase cholesterol efflux capacity of adipose tissue macrophages[J/OL]. Mol. Nutr. Food Res., 2019, 63(2): e1800713[2024-01-19]. .
43	MARSHALL J D, COURAGE E R, ELLIOTT R F, et al.. THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation[J/OL]. PLoS One, 2020, 15(5): e0233180[2024-01-19]. .
44	GUILLIAMS M, BONNARDEL J, HAEST B, et al.. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches[J]. Cell, 2022, 185(2): 379-396.e38.
45	FREDRICKSON G, FLORCZAK K, BARROW F, et al.. Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH[J/OL]. bioRxiv, 2023, doi: 10.1101/2023.06.11.544503[2024-01-19]. .
46	DAEMEN S, GAINULLINA A, KALUGOTLA G, et al.. Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH[J/OL]. Cell Rep., 2021, 34(2): 108626[2024-01-19]. .
47	SUN Q, NIU Q, GUO Y, et al.. Regulation on citrate influx and metabolism through inhibiting SLC13A5 and ACLY: a novel mechanism mediating the therapeutic effects of curcumin on NAFLD[J]. J. Agric. Food Chem., 2021, 69(31): 8714-8725.
48	WEI X, SONG H, YIN L, et al.. Fatty acid synthesis configures the plasma membrane for inflammation in diabetes[J]. Nature, 2016, 539(7628): 294-298.
49	SANTARSIERO A, CONVERTINI P, TODISCO S, et al.. ACLY nuclear translocation in human macrophages drives proinflammatory gene expression by NF-κB acetylation[J/OL]. Cells, 2021, 10(11): 2962[2024-01-19]. .
50	NAMGALADZE D, LIPS S, LEIKER T J, et al.. Inhibition of macrophage fatty acid β-oxidation exacerbates palmitate-induced inflammatory and endoplasmic reticulum stress responses[J]. Diabetologia, 2014, 57(5): 1067-1077.
51	MIYAO M, KAWAI C, KOTANI H, et al.. Mitochondrial fission in hepatocytes as a potential therapeutic target for nonalcoholic steatohepatitis[J]. Hepatol. Res., 2022, 52(12): 1020-1033.
52	STEFFEN J, NGO J, WANG S P, et al.. The mitochondrial fission protein Drp1 in liver is required to mitigate NASH and prevents the activation of the mitochondrial ISR[J/OL]. Mol. Metab., 2022, 64: 101566[2024-01-19]. .
53	PAN J, OU Z, CAI C, et al.. Fatty acid activates NLRP3 inflammasomes in mouse Kupffer cells through mitochondrial DNA release[J]. Cell Immunol., 2018, 332: 111-120.
54	GOIKOETXEA-USANDIZAGA N, SERRANO-MACIá M, DELGADO T C, et al.. Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals[J]. Hepatology, 2022, 75(3): 550-566.
55	LEE A H, OH J H, KIM H S, et al.. Peripheral blood mononuclear cell mitochondrial copy number and adenosine triphosphate inhibition test in NAFLD[J/OL]. Endocrinol. Lausanne., 2022, 13: 967848[2024-01-19]. .
56	ZEZINA E, SNODGRASS R G, SCHREIBER Y, et al.. Mitochondrial fragmentation in human macrophages attenuates palmitate-induced inflammatory responses[J]. Biochim. Biophys. Acta Mol. Cell Biol. Lipds, 2018, 1863(4): 433-446.

[1]	Yimiao ZHANG, Yuqin BIAN, Xinbo LIU, Jiahe PANG, Tongxuan SUN, Qiazheng DU, Wenhao XU, Tianze YIN, Hongshu SUI. Research Progress on the Cytotoxicity and Immune Effects of Carbon-based Nanomaterials [J]. Current Biotechnology, 2025, 15(4): 615-621.
[2]	Xiaoyu JIANG, Yi CHEN, Jingjing NI. Mechanism of miR-93 Regulating Immune-mediated Traumatic Brain Injury Through Activation of PI3K/AKT Pathway [J]. Current Biotechnology, 2025, 15(4): 711-719.
[3]	Xingpeng DUAN, Jingli LIU, Che WANG, Dejing SHANG. Effects of Macrophage Scavenger Receptors and Toll-like Receptors on Ox-LDL Uptake and Inflammation [J]. Current Biotechnology, 2024, 14(4): 668-675.
[4]	Li GAO, Lei YANG, Guangpeng LI. Research Progress on the Mechanism of Skeletal Muscle Development Stimulated by Myostatin Gene Mutation [J]. Current Biotechnology, 2021, 11(4): 476-482.
[5]	LU Yan1, CHEN Ying2, LU Qingming1, ZHANG Ying1, LI Zhaohui1, XIE Xiaohua1*. Alteration of Myocardial Macrophage Polarization Marker Proteins After Rat Traumatic Hemorrhagic Shock [J]. Curr. Biotech., 2017, 7(3): 225-229.

Research Progress on Glycolipid Metabolism Reprogramming of Macrophage in Non-alcoholic Fatty Liver Disease

巨噬细胞糖脂代谢重编程在非酒精性脂肪肝中的研究进展

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

References 56

Related Articles 5

Recommended Articles

Metrics

Comments