Small extracellular vesicles derived from lipotoxic hepatocytes transport FASN to promote hepatic stellate cell activation

Miao L, Targher G, Byrne CD, Cao YY, Zheng MH. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab. 2024. https://doi.org/10.1016/j.tem.2024.02.007

Article  PubMed  Google Scholar 

Bansal SK, Bansal MB. Review article: Pathogenesis of MASLD and MASH - role of insulin resistance and lipotoxicity. Aliment Pharmacol Ther. 2024. https://doi.org/10.1111/apt.17930

Article  PubMed  Google Scholar 

Zhao L, Tang H, Cheng Z. Pharmacotherapy of liver fibrosis and hepatitis: recent advances. Pharmaceuticals (Basel). 2024. https://doi.org/10.3390/ph17121724

Article  PubMed  PubMed Central  Google Scholar 

Dong J, Viswanathan S, Adami E, Singh BK, Chothani SP, Ng B, et al. Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH. Nat Commun. 2021;12:66

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xue T, Yam JWP. Role of small extracellular vesicles in liver diseases: pathogenesis, diagnosis, and treatment. J Clin Transl Hepatol. 2022;10:1176–1185

PubMed  PubMed Central  Google Scholar 

Jun JH, Du K, Dutta RK, Maeso-Diaz R, Oh SH, Wang L, et al. The senescence-associated secretome of hedgehog-deficient hepatocytes drives MASLD progression. J Clin Invest. 2024. https://doi.org/10.1172/JCI180310

Article  PubMed  PubMed Central  Google Scholar 

Garcia-Martinez I, Alen R, Pereira L, Povo-Retana A, Astudillo AM, Hitos AB, et al. Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance. JHEP Rep. 2023;5: 100756

Article  PubMed  PubMed Central  Google Scholar 

Li S, Yang F, Cheng F, Zhu L, Yan Y. Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy. Cell Mol Biol Lett. 2024;29:82

Article  PubMed  PubMed Central  Google Scholar 

Luo X, Xu ZX, Wu JC, Luo SZ, Xu MY. Hepatocyte-derived exosomal miR-27a activateshepatic stellate cells through the inhibitionof PINK1-mediated mitophagy in MAFLD. Mol Ther Nucleic Acids. 2021;26:1241–1254

Article  CAS  PubMed  PubMed Central  Google Scholar 

Du C, Zheng S, Yang Y, Feng X, Chen J, Tang Y, et al. Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder. Ecotoxicol Environ Saf. 2022;239: 113649

Article  CAS  PubMed  Google Scholar 

Nguyen P, Leray V, Diez M, Serisier S, Le Bloc’h J, Siliart B, et al. Liver lipid metabolism. J Anim Physiol Anim Nutr (Berl). 2008;92:272–283

Article  CAS  PubMed  Google Scholar 

Chu X, Hou Y, Peng C, Li W, Liang M, Mei J, et al. Exosome-derived miR-548ag drives hepatic lipid accumulation via upregulating FASN through inhibition of DNMT3B. J Lipid Res. 2025. https://doi.org/10.1016/j.jlr.2025.100818

Article  PubMed  PubMed Central  Google Scholar 

Dong L, Lou W, Xu C, Wang J. Naringenin cationic lipid-modified nanoparticles mitigate MASLD progression by modulating lipid homeostasis and gut microbiota. J Nanobiotechnology. 2025;23:168

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dai L, An D, Huang J, Xiao M, Li Z, Zhou B, et al. Ovarian multi-omics analysis reveals key rate-limiting enzymes FASN, SCD5, FADS1, 3BHSD, and STAR as potential targets for regulating kidding traits in goats. Int J Biol Macromol. 2024. https://doi.org/10.1016/j.ijbiomac.2024.136737

Article  PubMed  Google Scholar 

Su J, Fan X, Zou Y, Fu G, Feng S, Wang X, et al. Inhibition of aberrant activated fibroblast-like synoviocytes in rheumatoid arthritis by Leishmania peptide via the regulation of fatty acid synthesis metabolism. Adv Sci. 2025. https://doi.org/10.1002/advs.202409154

Article  Google Scholar 

Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol. 2016;65:579–588

Article  CAS  PubMed  PubMed Central  Google Scholar 

Welsh JA, Goberdhan DCI, O’Driscoll L, Buzas EI, Blenkiron C, Bussolati B, et al. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13: e12404

Article  PubMed  PubMed Central  Google Scholar 

Steinberg GR, Valvano CM, De Nardo W, Watt MJ. Integrative metabolism in MASLD and MASH: pathophysiology and emerging mechanisms. J Hepatol. 2025. https://doi.org/10.1016/j.jhep.2025.02.033

Article  PubMed  Google Scholar 

You H, Wang X, Ma L, Zhang F, Zhang H, Wang Y, et al. Insights into the impact of hepatitis B virus on hepatic stellate cell activation. Cell Commun Signal. 2023;21:70

Article  PubMed  PubMed Central  Google Scholar 

Cammisotto V, Valeriani E, Pignatelli P, Violi F. Nicotinamide adenine dinucleotide phosphate oxidases and metabolic dysfunction-associated steatotic liver disease. Antioxidants. 2025. https://doi.org/10.3390/antiox14010083

Article  PubMed  PubMed Central  Google Scholar 

Park GC, Bang SY, Kim JM, Shin SC, Cheon YI, Kim KM, et al. Inhibiting ferroptosis prevents the progression of steatotic liver disease in obese mice. Antioxidants. 2024. https://doi.org/10.3390/antiox13111336

Article  PubMed  PubMed Central  Google Scholar 

Svobodová G, Horní M, Velecká E, Boušová I. Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review. Arch Toxicol. 2024. https://doi.org/10.1007/s00204-024-03889-x

Article  PubMed  PubMed Central  Google Scholar 

Guo J, Ji Z, Jiang Y, Wu Y, Wang S, Zheng P, et al. Serpina3c deficiency promotes obesity-related hypertriglyceridemia and inflammation through activation of the Hif1α-glycolysis axis in adipose tissue. Clin Sci (Lond). 2025. https://doi.org/10.1042/CS20242610

Article  PubMed  Google Scholar 

Weng L, Tang WS, Wang X, Gong Y, Liu C, Hong NN, et al. Surplus fatty acid synthesis increases oxidative stress in adipocytes and lnduces lipodystrophy. Nat Commun. 2024;15:133

Article  CAS  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif