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Cited by 5Liver Disease Diagnosis and TreatmentLiver physiology and pathologyDrug Transport and Resistance Mechanisms

Deficiency of Epithelial PIEZO1 Alleviates Liver Steatosis Induced by High-Fat Diet in Mice

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Xu, Zhiyue, Xu, Shu, Liu, Xiaoming, Cheng, Lan, Liu, Xinghuang, Xie, Xiaotian, Zhou, Dan, Wang, Dongke +9 more·2025·International Journal of Biological Sciences
DOI 10.7150/ijbs.102906PMC PMC11705646
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Abstract

PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years.Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently.Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 (Piezo1 Δ IEC ) were used to explore the problem.IEC PIEZO1 deletion significantly alleviated liver steatosis, without change on glucose tolerance and energy expenditure.Fibroblast growth factor 15/19 (FGF15/19) was downregulated in IEC and portal vein of Piezo1 Δ IEC mice, which was associated with phenotypic change.After supplementary of exogenous FGF19, the effect of improving liver steatosis brought by PIEZO1 deletion was blocked.Notably, PIEZO1 depletion-induced FGF15 reduction was not dependent on classic bile acids (BAs) -farnesoid X receptor (FXR) pathway, but attributed to impaired retinol metabolism and lower content of retinoic acid (RA).Subsequently, addition of RA but not retinol benefited inducing FGF15 production in ileal organoid from Piezo1 Δ IEC mice.Altogether, IEC PIEZO1 represents a promising target for therapy of hepatic steatosis via the gut-liver axis.

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  1. [1]Rinella ME Lazarus JV Ratziu V Francque SM Sanyal AJ Kanwal F A multisociety Delphi consensus statement on new fatty liver disease nomenclature J Hepatol 2023 79 1542 56 37364790
  2. [2]Younossi ZM Golabi P Paik JM Henry A Van Dongen C Henry L The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review Hepatology 2023 77 1335 47 36626630 PMC10026948
  3. [3]Sheka AC Adeyi O Thompson J Hameed B Crawford PA Ikramuddin S Nonalcoholic Steatohepatitis: A Review JAMA 2020 323 1175 83 32207804
  4. [5]Tilg H Adolph TE Trauner M Gut-liver axis: Pathophysiological concepts and clinical implications Cell Metab 2022 34 1700 18 36208625
  5. [6]Tripathi A Debelius J Brenner DA Karin M Loomba R Schnabl B The gut-liver axis and the intersection with the microbiome Nat Rev Gastroenterol Hepatol 2018 15 397 411 29748586 PMC6319369
  6. [8]Carpi RZ Barbalho SM Sloan KP Laurindo LF Gonzaga HF Grippa PC The Effects of Probiotics, Prebiotics and Synbiotics in Non-Alcoholic Fat Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review Int J Mol Sci 2022 23 8805 35955942 PMC9369010
  7. [9]Ng CH Tang ASP Xiao J Wong ZY Yong JN Fu CE Safety and tolerability of obeticholic acid in chronic liver disease: a pooled analysis of 1878 individuals Hepatol Commun 2023 7 e0005 36757421 PMC9915961
  8. [10]Jiang Y Song J Xu Y Liu C Qian W Bai T Piezo1 regulates intestinal epithelial function by affecting the tight junction protein claudin-1 via the ROCK pathway Life Sci 2021 275 119254 33636174
  9. [11]Xu Y Bai T Xiong Y Liu C Liu Y Hou X Mechanical stimulation activates Piezo1 to promote mucin2 expression in goblet cells J Gastroenterol Hepatol 2021 36 3127 39 34169583
  10. [12]Eisenhoffer GT Loftus PD Yoshigi M Otsuna H Chien CB Morcos PA Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia Nature 2012 484 546 9 22504183 PMC4593481
  11. [13]Wang S Cao S Arhatte M Li D Shi Y Kurz S Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1/FGFR1 signaling pathway in mice Nat Commun 2020 11 2303 32385276 PMC7211025
  12. [14]Pan X Wan R Wang Y Liu S He Y Deng B Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B Br J Pharmacol 2022 179 3778 814 35194776
  13. [15]Ye Y Barghouth M Dou H Luan C Wang Y Karagiannopoulos A A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic beta-cells Nat Commun 2022 13 4237 35869052 PMC9307633
  14. [16]Kim YC Seok S Zhang Y Ma J Kong B Guo G Intestinal FGF15/19 physiologically repress hepatic lipogenesis in the late fed-state by activating SHP and DNMT3A Nat Commun 2020 11 5969 33235221 PMC7686350
  15. [17]Kir S Beddow SA Samuel VT Miller P Previs SF Suino-Powell K FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis Science 2011 331 1621 4 21436455 PMC3076083
  16. [18]Kim YC Byun S Seok S Guo G Xu HE Kemper B Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption Gastroenterology 2019 156 1052 65 30521806 PMC6409196
  17. [19]Byun S Kim DH Ryerson D Kim YC Sun H Kong B Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis Nat Commun 2018 9 2590 29968724 PMC6030054
  18. [20]Kleiner DE Brunt EM Van Natta M Behling C Contos MJ Cummings OW Design and validation of a histological scoring system for nonalcoholic fatty liver disease Hepatology 2005 41 1313 21 15915461
  19. [21]Bai T Xu Z Xia P Feng Y Liu B Liu H The Short-Term Efficacy of Bifidobacterium Quadruple Viable Tablet in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: Potentially Mediated by Metabolism Rather Than Diversity Regulation Am J Gastroenterol 2023 118 1256 67 36717369
  20. [22]Tan C Hong G Wang Z Duan C Hou L Wu J Promoting Effect of L-Fucose on the Regeneration of Intestinal Stem Cells through AHR/IL-22 Pathway of Intestinal Lamina Propria Monocytes Nutrients 2022 14 4789 36432480 PMC9695883
  21. [23]Fiorucci S Distrutti E Carino A Zampella A Biagioli M Bile acids and their receptors in metabolic disorders Prog Lipid Res 2021 82 101094 33636214
  22. [25]Cai J Sun L Gonzalez FJ Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis Cell Host Microbe 2022 30 289 300 35271802 PMC8923532
  23. [26]Kuang J Wang J Li Y Li M Zhao M Ge K Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis Cell Metab 2023 35 1752 66 e8 37591244
  24. [27]Wang H Chen J Hollister K Sowers LC Forman BM Endogenous bile acids are ligands for the nuclear receptor FXR/BAR Mol Cell 1999 3 543 53 10360171
  25. [28]Albarran-Juarez J Iring A Wang S Joseph S Grimm M Strilic B Piezo1 and G(q)/G(11) promote endothelial inflammation depending on flow pattern and integrin activation J Exp Med 2018 215 2655 72 30194266 PMC6170174
  26. [29]Zhao Y Liu Y Tao T Zhang J Guo W Deng H Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake Nat Metab 2024 6 458 72 38467889
  27. [30]Lang K Breer H Frick C Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach Cell Tissue Res 2018 371 251 60 29264643 PMC5784007
  28. [31]Sugisawa E Takayama Y Takemura N Kondo T Hatakeyama S Kumagai Y RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis Cell 2020 182 609 24 e21 32640190
  29. [32]Alvarez-Sola G Uriarte I Latasa MU Fernandez-Barrena MG Urtasun R Elizalde M Fibroblast growth factor 15/19 (FGF15/19) protects from diet-induced hepatic steatosis: development of an FGF19-based chimeric molecule to promote fatty liver regeneration Gut 2017 66 1818 28 28119353
  30. [34]Schumacher JD Kong B Pan Y Zhan L Sun R Aa J The effect of fibroblast growth factor 15 deficiency on the development of high fat diet induced non-alcoholic steatohepatitis Toxicol Appl Pharmacol 2017 330 1 8 28673684 PMC5812273
  31. [35]Wu X Ge H Baribault H Gupte J Weiszmann J Lemon B Dual actions of fibroblast growth factor 19 on lipid metabolism J Lipid Res 2013 54 325 32 23204296 PMC3588862
  32. [36]Inagaki T Choi M Moschetta A Peng L Cummins CL McDonald JG Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis Cell Metab 2005 2 217 25 16213224
  33. [37]Pullinger CR Eng C Salen G Shefer S Batta AK Erickson SK Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype J Clin Invest 2002 110 109 17 12093894 PMC151029
  34. [38]Chow EC Magomedova L Quach HP Patel R Durk MR Fan J Vitamin D receptor activation down-regulates the small heterodimer partner and increases CYP7A1 to lower cholesterol Gastroenterology 2014 146 1048 59 24365583
  35. [39]Li T Owsley E Matozel M Hsu P Novak CM Chiang JY Transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevents high-fat diet-induced obesity and insulin resistance in mice Hepatology 2010 52 678 90 20623580 PMC3700412
  36. [40]Gong R Lv X Liu F MiRNA-17 encoded by the miR-17-92 cluster increases the potential for steatosis in hepatoma cells by targeting CYP7A1 Cell Mol Biol Lett 2018 23 16 29721023 PMC5907481
  37. [41]Liu H Pathak P Boehme S Chiang JL Cholesterol 7alpha-hydroxylase protects the liver from inflammation and fibrosis by maintaining cholesterol homeostasis J Lipid Res 2016 57 1831 44 27534992 PMC5036364
  38. [42]Mangelsdorf DJ Evans RM The RXR heterodimers and orphan receptors Cell 1995 83 841 50 8521508
  39. [43]Zheng W Lu Y Tian S Ma F Wei Y Xu S Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR J Biol Chem 2018 293 12535 41 29934308 PMC6093246
  40. [44]Kim Y Lee S Kim S Kim TY Lee SH Chang JH LKB1 in Intestinal Epithelial Cells Regulates Bile Acid Metabolism by Modulating FGF15/19 Production Cell Mol Gastroenterol Hepatol 2022 13 1121 39 34973477 PMC8873961
  41. [45]Cai SY He H Nguyen T Mennone A Boyer JL Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR/RXR-dependent and independent mechanisms J Lipid Res 2010 51 2265 74 20338915 PMC2903807
  42. [46]Zhou M Luo J Chen M Yang H Learned RM DePaoli AM Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15 J Hepatol 2017 66 1182 92 28189755
  43. [47]Murphy KG Dhillo WS Bloom SR Gut peptides in the regulation of food intake and energy homeostasis Endocr Rev 2006 27 719 27 17077190
  44. [48]Wu AL Coulter S Liddle C Wong A Eastham-Anderson J French DM FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways PLoS One 2011 6 e17868 21437243 PMC3060878
  45. [49]Fu L John LM Adams SH Yu XX Tomlinson E Renz M Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes Endocrinology 2004 145 2594 603 14976145
  46. [50]Lan T Morgan DA Rahmouni K Sonoda J Fu X Burgess SC FGF19, FGF21, and an FGFR1/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia Cell Metab 2017 26 709 18 e3 28988823 PMC5679468
  47. [51]Monteiro MP Batterham RL The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance Gastroenterology 2017 152 1707 17 e2 28193513
  48. [52]Hsuchou H Pan W Kastin AJ Fibroblast growth factor 19 entry into brain Fluids Barriers CNS 2013 10 32 24176017 PMC3818657
  49. [53]Liu S Marcelin G Blouet C Jeong JH Jo YH Schwartz GJ A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus Mol Metab 2018 8 37 50 29290621 PMC5985052

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Authors
Xu, Z., Xu, S., Liu, X., Cheng, L., Liu, X., Xie, X., Zhou, D., Wang, D., Chen, J., Deng, X., Zhang, L., He, R., Li, Y., Cheng, M., Yang, L., Hou, X., & Bai, T.
Affiliations
Wuhan Union Hospital (CN)
Corresponding author
  • Xu, Zhiyue
  • Xu, Shu
ORCID
Venue
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Published
2025-01-01
Volume
21
Issue
2
Pages
745-757
ISSN
1449-2288 (ISSN-L)
DOI
10.7150/ijbs.102906
PMC
PMC11705646
OpenAlex
W4405953795
Cited by
5
References
4
Citations by year
2026: 4 · 2025: 1
FWCI
1.53
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • International Journal of Biological Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (92268108, 81900477, 82100561)
  • Huazhong University of Science and Technology
  • Jianghan University
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
Piezo1, intestinal epithelial cells, hepatic steatosis, high-fat diet, gut-liver axis, FGF15/19, vitamin A metabolism, retinoic acid, bile acids, farnesoid X receptor, intestinal barrier, hepatic lipid metabolism
MeSH terms
Animals, Epithelial Cells, Fatty Liver, Fibroblast Growth Factors, Ion Channels, Liver, Male, Mice, Inbred C57BL, Mice, Diet, High-Fat

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