Research progress on the mechanism of action of sterol regulatory element-binding protein(SREBP) in metabolic inflammatory syndrome

doi:10.16352/j.issn.1001-6325.2026.09.1287

Abstract

Abstract: Sterol regulatory element-binding proteins(SREBPs), key transcription factors in cellular lipid metabolism regulation, play a significant role in the development of metabolic inflammatory response syndrome(MIS). Under prolonged high-fat intake, aberrant expression levels of SREBPs contribute to the pathogenesis of MIS by modulating multiple signaling pathways, including uric acid metabolism, vascular endothelial cell(VEC) proliferation, immune cell activity, and NF-κB/NLRP3 signaling pathway. Furthermore, excessive activation of SREBPs leads to chronic inflammation and impairs the body's ability to regulate inflammation.

Key words: sterol regulatory element-binding protein(SREBP), metabolic inflammatory syndrome, gout, NLRP3 inflammasome, nuclear factor-κB(NF-κB)

CLC Number:

R589.2

ZHANG Yi, YANG Lijuan, WANG Pingle. Research progress on the mechanism of action of sterol regulatory element-binding protein(SREBP) in metabolic inflammatory syndrome[J]. Basic & Clinical Medicine, 2026, 46(9): 1287-1292.

References

[1] Wu Y,Song W,Su M,et al.The role of cholesterol metabolism and its regulation in tumor development[J].Cancer Med,2025,14:e70783.doi: 10.1002/cam4.70783.
[2] Barbhuiya PA,Yoshitomi R,Pathak MP.Understanding the link between sterol regulatory element binding protein(SREBPs)and metabolic dysfunction associated steatotic liver disease(MASLD)[J].Curr Obes Rep,2025,14:36.doi: 10.1007/s13679-025-00626-y.
[3] Bergentall M,Tremaroli V,Sun C,et al.Gut microbiota mediates SREBP-1c-driven hepatic lipogenesis and steatosis in response to zero-fat high-sucrose diet[J].Mol Metab,2025,97:102162.doi: 10.1016/j.molmet.
[4] Stachowicz A,Czepiel K,Wiśniewska A,et al.Mitochon-dria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways[J].Pharmacol Res,2024,209:107428.doi: 10.1016/j.phrs.2024.107428.
[5] Ouyang N,Gan H,He Q,et al.Dysfunction of cholesterol sensor SCAP promotes inflammation activation in THP-1 macrophages[J].Exp Cell Res,2018,367:162-169.
[6] Lee JH, Lee SH, Lee EH,et al.SCAP deficiency facilitates obesity and insulin resistance through shifting adipose tissue macrophage polarization[J].J Adv Res,2023,45:1-13.
[7] Zhang X,Liu J.Regulating lipid metabolism in gout:a new perspective with therapeutic potential[J].Int J Gen Med,2024,17:5203-5217.
[8] Kawamura S,Matsushita Y,Kurosaki S,et al.Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis[J].J Clin Invest,2022,132:e151895.doi: 10.1172/JCI151895.
[9] 黄艳,袁放.不同年龄段痛风发生代谢相关脂肪性肝病的影响因素研究[J].现代医药卫生,2025,41:65-67.
[10] Chen B,Bao R,Pan J,et al.Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR axis[J].J Lipid Res,2025,66:100746. doi: 10.1016/j.jlr.2025.100746.
[11] Zhou R,Stouffer GA,Frishman WH.Cholesterol paradigm and beyond in atherosclerotic cardiovascular disease:cholesterol,sterol regulatory element-binding protein,inflammation,and vascular cell mobilization in vasculopathy[J].Cardiol Rev,2022,30:267-273.
[12] Chen Z,Martin M,Li Z,et al.Endothelial dysfunction:the role of sterol regulatory element-binding protein-induced NOD-like receptor family pyrin domain-containing protein 3 inflammasome in atherosclerosis[J].Curr Opin Lipidol,2014,25:339-349.
[13] Zhao Z,Zhao Y,Zhang Y,et al.Gout-induced endothelial impairment:The role of SREBP2 transactivation of YAP[J].FASEB J,2021,35:e21613.doi: 10.1096/fj.202100337R.
[14] Cheng Y,Manabe I,Hayakawa S,et al.Caspase-11 contributes to site-1 protease cleavage and SREBP1 activation in the inflammatory response of macrophages[J].Front Immunol,2023,14:1009973.doi: 10.3389/fimmu.2023.1009973.
[15] Kusnadi A,Park S H,Yuan R,et al.The cytokine TNF promotes transcription factor SREBP activity and binding to Inflammatory genes to activate macrophages and limit tissue repair[J].Immunity,2019,51:241-257.
[16] Moretti J,Jia B,Hutchins Z,et al.Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome[J].Nat Immunol,2022,23:705-717.
[17] Luo W,Adamska J Z,Li C,et al.SREBP signaling is essential for effective B cell responses[J].Nat Immunol,2023,24:337-348.
[18] Xi Z,Shu L,Xiao L,et al.Macrophage NLRP3 inflammasome mediates the effects of sympathetic nerve on cardiac remodeling in obese rats[J].Mol Cell Endocrinol,2025,596:112417.doi: 10.1016/j.mce.2024.112417.
[19] Steffen TL,Stafford JD,Samson WK,et al.Nesfatin-1 is a regulator of inflammation with implications during obesity and metabolic syndrome[J].Appetite,2024,203:107669.doi: 10.1016/j.appet.2024.107669.
[20] Han N,Chang X,Yuan Z,et al.Expression and correlation analysis of silent information regulator 1(SIRT1),sterol regulatory element-binding protein-1(SREBP1),and pyroptosis factor in gestational diabetes mellitus[J].J Matern Fetal Neonatal Med,2024,37:2311809.doi:10.1080/14767058.2024.2311809.
[21] Varghese JF,Patel R,Yadav UCS.Sterol regulatory element binding protein(SREBP)-1 mediates oxidized low-density lipoprotein(oxLDL)induced macrophage foam cell formation through NLRP3 inflammasome activation[J].Cell Signal,2019,53:316-326.
[22] Guo C,Chi Z,Jiang D,et al.Cholesterol homeostatic regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome activation and cholesterol biosynthetic signaling in macrophages[J].Immunity,2018,49:842-856.
[23] Fei X,Huang J,Li F,et al.The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-kappaB[J].Cell Rep,2023,42:112586.doi: 10.1016/j.celrep.2023.112586.
[24] Hao K,Jiang W,Zhou M,et al.Erratum:Targeting BRD4 prevents acute gouty arthritis by regulating pyroptosis:Erratum[J].Int J Biol Sci,2025,21:473-474.