KLF4通过抑制脂肪酸合成抑制MASLD的发生

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中图分类号：R575.5 文献标志码：A

KLF4 suppresses MASLD progression via inhibiting fatty acid synthesis

CHEN Yuting，FAN Lijun，PAN Ziyan，WANG Cuizhe，ZHANG Ting，ZHANG Jun* （SchoolfMedicine/KeyLaboratoryofXinjiangEndemicandEtnicDisease，SiheziUniversity，Shihezi，Xijiang832hia

Abstract：ObjectiveToinvestigatetheroleofKLF4inthedevelopmentofmetabolicdsfunction-associatedsteatoticliverdisease （MASLD）andtopreliminarily explore itspossible molecularmechanisms.Methods Twelve C57BL/6malemice weredivided intoa normal diet group（ND， n=6 ）andahigh fatdiet group（HFD， n=6 ），and theirbodyweightwere monitored.Theprotein expression levelandmRNAexpresionlevelofKLF4inliverissueswereanalyzed.Acellmodelof lipidmetabolismdisorderswasconsructedusingfreefattyacid（FFA）treatmentofhumanhepatocellarcarcinomacellsHepG2andmousehepatocellarcarciomacellsHepal -6 .Theinvitro experiments weredividedintotheOE-KLF4-FFAanditscontrolNC-FFAgroup，andtheSi-KLF4-FFAanditscontrolNC-FFAgroup.Thelevelsof intracelllartrglyceride（TG）andcholesterol（CHO）weredetectedbyenzymeassayTemRNA andproteinexpressonlevelsofKLF4，lipidsynthesisfattyacidsynthase（FASN），sterolregulatoryelementbindingprotein1 （SREBP1），and peroxisome proliferator-activated receptor γ （ PPARγ ）were analyzed by real-time fluorescence quantitative polymerasechainreactionndwesteblotingassayespectivelyResultsTheproteinandRAexpresionlevesofKLF4intelivertissuesof miceinthe HFDgroup were significantlylower than those intheNDgroup，whereasthemRNAexpresionlevelsofFASN， SREBP1，and PPARγ were significantly higher compared with the ND group.（ P<0.05 P<0.01 ， P<0.001 ）.FFA treatment of

HepG2 cells and Hepal-6 cells resulted in decreased mRNA and protein expression levels of KLF4（ P<0.05，P<0.01 .OverexpressionofKLF4reducedlipidacumulationanddecreasedmRNAandproteinexpressonlevelsofipidsyesisrelatedfactorsHepG2 cellsand Hepal-6 cells（ P<0.05 ， P<0.01 P<0. 001 ）.Knockdown ofKLF4 exacerbated lipidaccumulationand increased mRNA and protein expression levels of lipid synthesis related factors in HepG2 cellsand Hepal-6 cells（ P<0.05 ， P/<0.01 ， P<0.001 ）. Conclusion KLF4 suppresses MASLD by inhibiting fatty acid synthesis.

非酒精性脂肪性肝病（Non-alcoholicfattyliverdisease，NAFLD）现更名为代谢功能障碍相关脂肪变性肝病（Metabolic dysfunction-associated steatoticliverdisease，MASLD），是以肝实质脂肪细胞大量堆积以及脂肪变性为主要特征的疾病，研究表明MASLD会从单纯脂肪变性发展到非酒精性脂肪性肝炎、肝硬化甚至肝癌[1-2]。（剩余11379字）