AMP依赖的蛋白激酶调节脂质积累治疗非酒精性脂肪肝病的治疗研究进展

doi:10.3969/j.issn.1006-5725.2024.06.022

Abstract

Abstract:

Non?alcoholic fatty liver disease （NAFLD） is the leading cause of chronic liver disease and has posed significant challenges to global public health and medical care. Due to the unclear pathogenesis of NAFLD， lipid accumulation plays a key role in its development. AMPK， as a crucial molecule in lipid metabolism regulation， can improve lipid accumulation caused by NAFLD. This article describes the specific mechanisms of AMPK?related molecules in improving lipid accumulation and treating NAFLD， and lists the current experimental and therapeutic drugs related to AMPK. The potential of AMPK?related drugs in improving lipid accumulation and treating NAFLD is demonstrated， providing ideas and references for future research on AMPK?related drugs for treating NAFLD.

Key words: non?alcoholic fatty liver disease, AMPK, lipid metabolism, clinical treatment

CLC Number:

R575.5

Pengshuai SUN,Feng ZHU,Lihong ZHENG,Haiqiang WANG. Research progress in the treatment of AMPK regulating lipid accumulation in the treatment of nonalcoholic fatty liver disease[J]. The Journal of Practical Medicine, 2024, 40(6): 862-866.

Figures/Tables 1

References 44

1	POWELL E E ， WONG V W S ， RINELLA M . Non-alcoholic fatty liver disease［J］. Lancet， 2021， 397（10290）： 2212-2224. doi:10.1016/s0140-6736(20)32511-3 doi: 10.1016/s0140-6736(20)32511-3
2	MANTOVANI A ， DALBENI A . Recent Developments in NAFLD［J］. Int J Mol Sci， 2022， 23（5）： 2882. doi:10.3390/ijms23052882 doi: 10.3390/ijms23052882
3	ZHOU J ， ZHENG Q ， CHEN Z . The Nrf2 pathway in liver diseases［J］. Front Cell Dev Biol， 2022， 10： 826204. doi:10.3389/fcell.2022.826204 doi: 10.3389/fcell.2022.826204
4	CAROTTI S ， AQUILANO K ， VALENTINI F ， et al . An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase［J］.Am J Physiol Gastrointest Liver Physiol， 2020， 319（4）： G469-G480. doi:10.1152/ajpgi.00049.2020 doi: 10.1152/ajpgi.00049.2020
5	XU X ， POULSEN K L ， WU L ， et al . Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis （NAFL/NASH）［J］. Signal Transduct Target Ther， 2022， 7（1）： 287. doi:10.1038/s41392-022-01119-3 doi: 10.1038/s41392-022-01119-3
6	SVEGLIATI-BARONI G ， PIERANTONELLI I ， TORQUATO P ， et al . Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease［J］. Free Radic Biol Med， 2019， 144： 293-309. doi:10.1016/j.freeradbiomed.2019.05.029 doi: 10.1016/j.freeradbiomed.2019.05.029
7	PEI K ， GUI T ， KAN D ， et al . An overview of lipid metabolism and nonalcoholic fatty liver disease［J］. Biomed Res Int， 2020， 4020249. doi:10.1155/2020/4020249 doi: 10.1155/2020/4020249
8	FELDSTEIN A E . Novel insights into the pathophysiology of nonalcoholic fatty liver disease［C］， Semin Liver Dis，2010，30（4）：391-401. doi:10.1055/s-0030-1267539 doi: 10.1055/s-0030-1267539
9	CASAGRANDE B P ， DE SOUZA D V ， RIBEIRO D A ， et al . Hepatic inflammation precedes steatosis and is mediated by visceral fat accumulation［J］. Endocrinol， 2020， 245（3）： 369-380. doi:10.1530/joe-20-0073 doi: 10.1530/joe-20-0073
10	MARRA F ， SVEGLIATI-BARONI G . Lipotoxicity and the gut-liver axis in NASH pathogenesis［J］， Hepatol， 2018， 68（2）： 280-295. doi:10.1016/j.jhep.2017.11.014 doi: 10.1016/j.jhep.2017.11.014
11	SUZUKI A ， DIEHL A M . Nonalcoholic steatohepatitis［J］. Annu Rev Med， 2017， 68： 85-98. doi:10.1146/annurev-med-051215-031109 doi: 10.1146/annurev-med-051215-031109
12	PIERANTONELLI I ， SVEGLIATI-BARONI G . Nonalcoholic fatty liver disease： basic pathogenetic mechanisms in the progression from NAFLD to NASH［J］. Transplantation， 2019， 103（1）： e1-e13. doi:10.1097/tp.0000000000002480 doi: 10.1097/tp.0000000000002480
13	GASTALDELLI A . Insulin resistance and reduced metabolic flexibility： cause or consequence of NAFLD？［J］. Clin Sci （Lond），2017，131（22）：2701-2704. doi:10.1042/cs20170987 doi: 10.1042/cs20170987
14	JEON S M . Regulation and function of AMPK in physiology and diseases［J］. Exp Mol Med， 2016， 48（7）： e245-e245. doi:10.1038/emm.2016.81 doi: 10.1038/emm.2016.81
15	FANG C ， PAN J ， QU N ， et al . The AMPK pathway in fatty liver disease［J］. Front Physiol， 2022，13：970292. doi:10.3389/fphys.2022.970292 doi: 10.3389/fphys.2022.970292
16	HARDIE D G ， ROSS F A ， HAWLEY S A . AMPK： a nutrient and energy sensor that maintains energy homeostasis［J］. Nat Rev Mol Cell Biol， 2012，13（4）：251-262. doi:10.1038/nrm3311 doi: 10.1038/nrm3311
17	CARLING D . AMPK hierarchy： a matter of space and time［J］. Cell Res， 2019，29（6）：425-426. doi:10.1038/s41422-019-0171-6 doi: 10.1038/s41422-019-0171-6
18	SMITH B K ， MARCINKO K ， DESJARDINS E M ， et al . Treatment of nonalcoholic fatty liver disease： role of AMPK［J］. Am J Physiol Endocrinol Metab， 2016， 311（4）： E730-E740. doi:10.1152/ajpendo.00225.2016 doi: 10.1152/ajpendo.00225.2016
19	HOPPE S ， BIERHOFF H ， CADO I ， et al . AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply［J］. Proc Natl Acad Sci U S A.， 2009，106（42）：17781-17786. doi:10.1073/pnas.0909873106 doi: 10.1073/pnas.0909873106
20	AMEER F ， SCANDIUZZI L ， HASNAIN S ， et al . De novo lipogenesis in health and disease［J］. Metabolism， 2014，63（7）：895-902. doi:10.1016/j.metabol.2014.04.003 doi: 10.1016/j.metabol.2014.04.003
21	ZANG M ， ZUCCOLLO A ， HOU X ， et al . AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells［J］. Biol Chem， 2004，279（46）：47898-47905. doi:10.1074/jbc.m408149200 doi: 10.1074/jbc.m408149200
22	CHEN Y ， HE X ， CHEN X ， et al . SeP is elevated in NAFLD and participates in NAFLD pathogenesis through AMPK/ACC pathway［J］. J Cell Physiol， 2021，236（5）：3800-3807. doi:10.1002/jcp.30121 doi: 10.1002/jcp.30121
23	ADEVA-ANDANY M M ， CARNEIRO-FREIRE N ， SECO-FILGUEIRA M ， et al . Mitochondrial β-oxidation of saturated fatty acids in humans［J］. Mitochondrion， 2019，46：73-90. doi:10.1016/j.mito.2018.02.009 doi: 10.1016/j.mito.2018.02.009
24	TIAN L I ， CAO W ， YUE R ， et al . Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia/reperfusion injury via AMPK/SIRT1/PGC-1 alpha signaling pathway［J］. J Pharmacol Sci， 2019，139（4）：352-360. doi:10.1016/j.jphs.2019.02.008 doi: 10.1016/j.jphs.2019.02.008
25	UENO T ， KOMATSU M . Autophagy in the liver： functions in health and disease［J］. Gastroenterol Hepatol， 2017，14（3）：170-184. doi:10.1038/nrgastro.2016.185 doi: 10.1038/nrgastro.2016.185
26	SHI C ， XUE W ， HAN B ， et al . Acetaminophen aggravates fat accumulation in NAFLD by inhibiting autophagy via the AMPK/mTOR pathway［J］. Eur J Pharmacol， 2019，850：15-22. doi:10.1016/j.ejphar.2019.02.005 doi: 10.1016/j.ejphar.2019.02.005
27	IERSHOV A ， NEMAZANYY I ， AYLKHOURY C ， et al . The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα［J］. Nat Commun， 2019，10（1）：1566. doi:10.1038/s41467-019-09598-9 doi: 10.1038/s41467-019-09598-9
28	HERZIG S ， SHAW R J . AMPK： guardian of metabolism and mitochondrial homeostasis［J］. Nat Rev Mol Cell Biol， 2018，19（2）：121-135. doi:10.1038/nrm.2017.95 doi: 10.1038/nrm.2017.95
29	BAI Y ， LI T ， LIU J ， et al . Aerobic exercise and vitamin E improve high-fat diet-induced NAFLD in rats by regulating the AMPK pathway and oxidative stress［J］. Eur J Nutr， 2023，62（6）：2621-2632. doi:10.1007/s00394-023-03179-9 doi: 10.1007/s00394-023-03179-9
30	CHEN K ， CHEN X ， XUE H ， et al . Coenzyme Q10 attenuates high-fat diet-induced non-alcoholic fatty liver disease through activation of the AMPK pathway［J］. Food Funct， 2019，10（2）：814-823. doi:10.1039/c8fo01236a doi: 10.1039/c8fo01236a
31	DUSABIMANA T ， PARK E J ， JE J， et al . P2y2r deficiency ameliorates hepatic steatosis by reducing lipogenesis and enhancing fatty acid β-oxidation through ampk and pgc-1α induction in high-fat diet-fed mice［J］. Int J Mol Sci， 2021，22（11）：5528. doi:10.3390/ijms22115528 doi: 10.3390/ijms22115528
32	ILBEIGI D ， NOURBAKHSH M ， PASALAR P ， et al . Nicotinamide phosphoribosyltransferase knockdown leads to lipid accumulation in HepG2 cells through the SIRT1-AMPK pathway［J］. Cell J， 2020，22（）：125-132.
33	ZHANG Y ， DENG Y ， TANG K ， et al . Berberine ameliorates high-fat diet-induced non-alcoholic fatty liver disease in rats via activation of SIRT3/AMPK/ACC pathway［J］. Curr Med Sci， 2019， 39（1）： 37-43. doi:10.1007/s11596-019-1997-3 doi: 10.1007/s11596-019-1997-3
34	LIN W ， JIN Y ， HU X ， et al . AMPK/PGC-1α/GLUT4-mediated effect of icariin on hyperlipidemia-induced non-alcoholic fatty liver disease and lipid metabolism disorder in mice［J］. Biochemistry （Mosc）， 2021，86（11）：1407-1417. doi:10.1134/s0006297921110055 doi: 10.1134/s0006297921110055
35	CHEN H ， NIE T ， ZHANG P ， et al . Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation［J］. Life Sci， 2022，296：120428. doi:10.1016/j.lfs.2022.120428 doi: 10.1016/j.lfs.2022.120428
36	LIU X ， HU M ， YE C ， et al . Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway［J］. Chem Biol Interact， 2022，368：110250. doi:10.1016/j.cbi.2022.110250 doi: 10.1016/j.cbi.2022.110250
37	ZHANG M ， YUAN Y ， WANG Q ， et al . The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα［J］.Biosci Rep， 2018，38（6）：BSR20180644. doi:10.1042/bsr20180644 doi: 10.1042/bsr20180644
38	ZHU M ， HAO S ， LIU T ， et al . Lingguizhugan decoction improves non-alcoholic fatty liver disease by altering insulin resistance and lipid metabolism related genes： a whole trancriptome study by RNA-Seq［J］. Oncotarget， 2017，8（47）：82621-82631. doi:10.18632/oncotarget.19734 doi: 10.18632/oncotarget.19734
39	MENG Z ， LIU X ， LI T ， et al . The SGLT2 inhibitor empagliflozin negatively regulates IL-17/IL-23 axis-mediated inflammatory responses in T2DM with NAFLD via the AMPK/mTOR/autophagy pathway［J］. Int Immunopharmacol， 2021，94：107492. doi:10.1016/j.intimp.2021.107492 doi: 10.1016/j.intimp.2021.107492
40	KRISHNAN A ， VISWANATHAN P ， VENKATARAMAN A C . AMPK activation by AICAR reduces diet induced fatty liver in C57BL/6 mice［J］. Tissue Cell， 2023，82：102054. doi:10.1016/j.tice.2023.102054 doi: 10.1016/j.tice.2023.102054
41	CHEN S ， LUO S ， ZUO B ， et al . Magnesium supplementation stimulates autophagy to reduce lipid accumulation in hepatocytes via the AMPK/mTOR pathway［J］. Biol Trace Elem Res， 2023，201（7）：3311-3322. doi:10.1007/s12011-022-03438-6 doi: 10.1007/s12011-022-03438-6
42	HE Y ， AO N ， YANG J ， et al . The preventive effect of liraglutide on the lipotoxic liver injury via increasing autophagy［J］. Ann Hepatol， 2020，19（1）：44-52. doi:10.1016/j.aohep.2019.06.023 doi: 10.1016/j.aohep.2019.06.023
43	YAN L S ， ZHANG S F ， LUO G ， et al . Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway［J］. Metabolism， 2022，131：155200. doi:10.1016/j.metabol.2022.155200 doi: 10.1016/j.metabol.2022.155200
44	ZHANG J ， DU H ， SHEN M ， et al . Kangtaizhi granule alleviated nonalcoholic fatty liver disease in high-fat diet-fed rats and HepG2 cells via AMPK/mTOR signaling pathway［J］. Immunol Res， 2020，2020：3413186. doi:10.1155/2020/3413186 doi: 10.1155/2020/3413186

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Research progress in the treatment of AMPK regulating lipid accumulation in the treatment of nonalcoholic fatty liver disease

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