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Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids

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Abstract

Fatty liver disease has grown into a major global health burden, attributed to multi-factors including sedentary lifestyle, obesogenic diet and prevalence of metabolic disorders. The lack of robust experimental models is hampering the research and therapeutic development for fatty liver disease. This study aims to develop an organoid-based 3D culture model to recapitulate key features of fatty liver disease focusing on intracellular lipid accumulation and metabolic dysregulation. We used human liver-derived intrahepatic cholangiocyte organoids and hepatocyte differentiated organoids. These organoids were exposed to lactate, pyruvate, and octanoic acid (LPO) for inducing lipid accumulation and mitochondrial impairment. Lipid accumulation resulted in alternations of gene transcription with major effects on metabolic pathways, including triglyceride and glucose level increase, which is consistent with metabolic changes in fatty liver disease patients. Interestingly, lipid accumulation affected mitochondria as shown by morphological transitions, alternations in expression of mitochondrial encoded genes, and reduction of ATP production. Meanwhile, we found treatment with obeticholic acid and metformin can alleviate fat accumulation in organoids. This study demonstrated that LPO exposure can induce lipid accumulation and associated metabolic dysregulation in human liver-derived organoids. This provides an innovative model for studying fatty liver disease and testing potential therapeutics.

Key messages

  • Lactate, pyruvate, and octanoic acid induce lipid accumulation in liver organoids.

  • Organoids of human compared to mouse origin are more efficient in lipid accumulation.

  • Lipid accumulation dysregulates metabolic pathway and impairs mitochondrial function.

  • Demonstrating a proof-of-concept for testing medications in organoids.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

MAFLD:

Metabolic dysfunction associated fatty liver disease

ICOs:

Intrahepatic cholangiocyte organoids

LPO:

Lactate, pyruvate, and octanoic acid

TMRM:

Tetramethylrhodamine

PLIN 1:

Perilipin 1

PLIN2:

Perilipin 2

PPARα:

Peroxisome proliferator-activated receptor alpha

CPT1A:

Carnitine palmitoyltransferase 1A

PCK1:

Phosphoenolpyruvate carboxykinase 1

G6PC:

Glucose-6-phosphatase

HSD17B13:

17β-Hydroxysteroid dehydrogenase type 13

CHREBP:

Carbohydrate-responsive element-binding protein

LXR α:

Liver X receptor alpha

TGFB1:

Transforming growth factor beta 1

SCL25A4:

Solute carrier family 25, member 4

PGC1 α:

Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha

OXPHOS:

Oxidative phosphorylation

ATP:

Adenosine triphosphate

CK7:

Cytokeratin 7

CK19:

Cytokeratin 19

HNF4α:

Hepatocyte nuclear factor 4 alpha

OCT4:

Octamer-binding transcription factor 4

LGR5:

Leucine-rich repeat containing G protein-coupled receptor 5

B2M:

Beta2-microglobulin

References

  1. Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285. https://doi.org/10.1111/j.1365-2036.2011.04724.x

    Article  PubMed  CAS  Google Scholar 

  2. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, Zelber-Sagi S, Wong VWS, Dufour J-F, Schattenberg JM et al (2020) A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol 73:202–209. https://doi.org/10.1016/j.jhep.2020.03.039

    Article  PubMed  Google Scholar 

  3. Wang L, Liu J, Miao Z, Pan Q, Cao W (2021) Lipid droplets and their interactions with other organelles in liver diseases. Int J Biochem Cell Biol 133:105937. https://doi.org/10.1016/j.biocel.2021.105937

    Article  PubMed  CAS  Google Scholar 

  4. Yang P, Wang Y, Tang W, Sun W, Ma Y, Lin S, Jing J, Jiang L, Shi H, Song Z et al (2020) Western diet induces severe nonalcoholic steatohepatitis, ductular reaction, and hepatic fibrosis in liver CGI-58 knockout mice. Sci Rep 10:4701. https://doi.org/10.1038/s41598-020-61473-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Lockman KA, Htun V, Sinha R, Treskes P, Nelson LJ, Martin SF, Rogers SM, Le Bihan T, Hayes PC, Plevris JN (2016) Proteomic profiling of cellular steatosis with concomitant oxidative stress in vitro. Lipids Health Dis 15:114. https://doi.org/10.1186/s12944-016-0283-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Yu K, Chen B, Aran D, Charalel J, Yau C, Wolf DM, van’t Veer LJ, Butte AJ, Goldstein T, Sirota M (2019) Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types. Nat Commun 10:3574. https://doi.org/10.1038/s41467-019-11415-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Ouchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, Thompson W, Karns RA, Mayhew CN, McGrath PS et al (2019) Modeling steatohepatitis in humans with pluripotent stem cell-derived organoids. Cell Metab 30:374–384. https://doi.org/10.1016/j.cmet.2019.05.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Ramli MNB, Lim YS, Koe CT, Demircioglu D, Tng W, Gonzales KAU, Tan CP, Szczerbinska I, Liang H, Soe EL et al (2020) Human pluripotent stem cell-derived organoids as models of liver disease. Gastroenterology 159:1471–1486. https://doi.org/10.1053/j.gastro.2020.06.010

    Article  PubMed  CAS  Google Scholar 

  9. Dutta D, Heo I, Clevers H (2017) Disease modeling in stem cell-derived 3D organoid systems. Trends Mol Med 23:393–410. https://doi.org/10.1016/j.molmed.2017.02.007

    Article  PubMed  CAS  Google Scholar 

  10. Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen Monique MA, Ellis E, van Wenum M, Fuchs Sabine A, de Ligt J et al (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160:299–312. https://doi.org/10.1016/j.cell.2014.11.050

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Cao W, Chen K, Bolkestein M, Yin Y, Verstegen MMA, Bijvelds MJC, Wang W, Tuysuz N, ten Berge D, Sprengers D et al (2017) Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury. Gastroenterology 153:1133–1147. https://doi.org/10.1053/j.gastro.2017.07.006

    Article  PubMed  Google Scholar 

  12. Verstegen MMA, Roos FJM, Burka K, Gehart H, Jager M, de Wolf M, Bijvelds MJC, de Jonge HR, Ardisasmita AI, van Huizen NA et al (2020) Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease. Sci Rep 10:21900. https://doi.org/10.1038/s41598-020-79082-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Marsee A, Roos FJM, Verstegen MMA, Marsee A, Roos F, Verstegen M, Clevers H, Vallier L, Takebe T, Huch M et al (2021) Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell 28:816–832. https://doi.org/10.1016/j.stem.2021.04.005

    Article  PubMed  CAS  Google Scholar 

  14. Hu H, Gehart H, Artegiani B, Löpez-Iglesias C, Dekkers F, Basak O, van Es J, de Sousa Lopes SMC, Begthel H, Korving J et al (2018) Long-term expansion of functional mouse and human hepatocytes as 3D organoids. Cell 175:1591–1606. https://doi.org/10.1016/j.cell.2018.11.013

    Article  PubMed  CAS  Google Scholar 

  15. Broutier L, Andersson-Rolf A, Hindley CJ, Boj SF, Clevers H, Koo B-K, Huch M (2016) Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat Protoc 11:1724–1743. https://doi.org/10.1038/nprot.2016.097

    Article  PubMed  CAS  Google Scholar 

  16. Lyall MJ, Cartier J, Thomson JP, Cameron K, Meseguer-Ripolles J, O’Duibhir E, Szkolnicka D, Villarin BL, Wang Y, Blanco GR et al (2018) Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells. Philos Trans R Soc Lond B Biol Sci 373:20170362. https://doi.org/10.1098/rstb.2017.0362

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, Bhanot S, Monia BP, Li Y-X, Diehl AM (2007) Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45:1366–1374. https://doi.org/10.1002/hep.21655

    Article  PubMed  CAS  Google Scholar 

  18. Suppli MP, Rigbolt KTG, Veidal SS, Heebøll S, Eriksen PL, Demant M, Bagger JI, Nielsen JC, Oró D, Thrane SW et al (2019) Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals. Am J Physiol Gastrointest Liver Physiol 316:G462–G472. https://doi.org/10.1152/ajpgi.00358.2018

    Article  PubMed  CAS  Google Scholar 

  19. Rector RS, Thyfault JP, Uptergrove GM, Morris EM, Naples SP, Borengasser SJ, Mikus CR, Laye MJ, Laughlin MH, Booth FW et al (2010) Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol 52:727–736. https://doi.org/10.1016/j.jhep.2009.11.030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Dornas W, Schuppan D (2020) Mitochondrial oxidative injury: a key player in nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol 319:G400–G411. https://doi.org/10.1152/ajpgi.00121.2020

    Article  PubMed  CAS  Google Scholar 

  21. Jiao Y, Lu Y, Li X-Y (2015) Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacol Sin 36:44–50. https://doi.org/10.1038/aps.2014.116

    Article  PubMed  CAS  Google Scholar 

  22. de Oliveira MC, Gilglioni EH, de Boer BA, Runge JH, de Waart DR, Salgueiro CL, Ishii-Iwamoto EL, Oude Elferink RPJ, Gaemers IC (2016) Bile acid receptor agonists INT747 and INT777 decrease oestrogen deficiency-related postmenopausal obesity and hepatic steatosis in mice. Biochim Biophys Acta Mol Basis Dis 1862:2054–2062. https://doi.org/10.1016/j.bbadis.2016.07.012

    Article  CAS  Google Scholar 

  23. Brandt A, Hernández-Arriaga A, Kehm R, Sánchez V, Jin CJ, Nier A, Baumann A, Camarinha-Silva A, Bergheim I (2019) Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine. Sci Rep 9:6668. https://doi.org/10.1038/s41598-019-43228-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Verbeke L, Farre R, Trebicka J, Komuta M, Roskams T, Klein S, Elst IV, Windmolders P, Vanuytsel T, Nevens F et al (2014) Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology 59:2286–2298. https://doi.org/10.1002/hep.26939

    Article  PubMed  CAS  Google Scholar 

  25. Kajbaf F, De Broe ME, Lalau J-D (2016) Therapeutic concentrations of metformin: a systematic review. Clin Pharmacokinet 55:439–459. https://doi.org/10.1007/s40262-015-0323-x

    Article  PubMed  CAS  Google Scholar 

  26. Kinaan M, Ding H, Triggle CR (2015) Metformin: an old drug for the treatment of diabetes but a new drug for the protection of the endothelium. Med Princ Pract 24:401–415. https://doi.org/10.1159/000381643

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gómez-Lechón MJ, Donato MT, Martínez-Romero A, Jiménez N, Castell JV, O’Connor J-E (2007) A human hepatocellular in vitro model to investigate steatosis. Chem Biol Interact 165:106–116. https://doi.org/10.1016/j.cbi.2006.11.004

    Article  PubMed  CAS  Google Scholar 

  28. Michaut A, Le Guillou D, Moreau C, Bucher S, McGill MR, Martinais S, Gicquel T, Morel I, Robin M-A, Jaeschke H et al (2016) A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen. Toxicol Appl Pharmacol 292:40–55. https://doi.org/10.1016/j.taap.2015.12.020

    Article  PubMed  CAS  Google Scholar 

  29. Takahara I, Akazawa Y, Tabuchi M, Matsuda K, Miyaaki H, Kido Y, Kanda Y, Taura N, Ohnita K, Takeshima F et al (2017) Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice. PLoS One 12:e0170591. https://doi.org/10.1371/journal.pone.0170591

    Article  CAS  Google Scholar 

  30. Graffmann N, Ring S, Kawala M-A, Wruck W, Ncube A, Trompeter H-I, Adjaye J (2016) Modeling nonalcoholic fatty liver disease with human pluripotent stem cell-derived immature hepatocyte-like cells reveals activation of PLIN2 and confirms regulatory functions of peroxisome proliferator-activated receptor alpha. Stem Cells Dev 25:1119–1133. https://doi.org/10.1089/scd.2015.0383

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Pera MF (2011) The dark side of induced pluripotency. Nature 471:46–47. https://doi.org/10.1038/471046a

    Article  PubMed  CAS  Google Scholar 

  32. Liang G, Zhang Y (2013) Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell 13:149–159. https://doi.org/10.1016/j.stem.2013.07.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Guo W, Choi JK, Kirkland JL, Corkey BE, Hamilton JA (2000) Esterification of free fatty acids in adipocytes: a comparison between octanoate and oleate. Biochem J 349:463–471. https://doi.org/10.1042/0264-6021:3490463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kruitwagen HS, Oosterhoff LA, Vernooij IGWH, Schrall IM, van Wolferen ME, Bannink F, Roesch C, van Uden L, Molenaar MR, Helms JB et al (2017) Long-term adult feline liver organoid cultures for disease modeling of hepatic steatosis. Stem Cell Rep 8:822–830. https://doi.org/10.1016/j.stemcr.2017.02.015

    Article  CAS  Google Scholar 

  35. Prior N, Inacio P, Huch M (2019) Liver organoids: from basic research to therapeutic applications. Gut 68:2228. https://doi.org/10.1136/gutjnl-2019-319256

    Article  PubMed  CAS  Google Scholar 

  36. Nobili V, Carpino G, Alisi A, Franchitto A, Alpini G, De Vito R, Onori P, Alvaro D, Gaudio E (2012) Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease. Hepatology 56:2142–2153. https://doi.org/10.1002/hep.25742

    Article  PubMed  CAS  Google Scholar 

  37. Paku S, Nagy P, Kopper L, Thorgeirsson SS (2004) 2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: Confocal and electron microscopic studies. Hepatology 39:1353–1361. https://doi.org/10.1002/hep.20178

    Article  PubMed  CAS  Google Scholar 

  38. Raven A, Lu W-Y, Man TY, Ferreira-Gonzalez S, O’Duibhir E, Dwyer BJ, Thomson JP, Meehan RR, Bogorad R, Koteliansky V et al (2017) Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547:350–354. https://doi.org/10.1038/nature23015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Clémot M, Sênos Demarco R, Jones DL (2020) Lipid mediated regulation of adult stem cell behavior. Front Cell Dev Biol 8:115. https://doi.org/10.3389/fcell.2020.00115

    Article  PubMed  PubMed Central  Google Scholar 

  40. Li J, Cui Z, Zhao S, Sidman RL (2007) Unique glycerophospholipid signature in retinal stem cells correlates with enzymatic functions of diverse long-chain acyl-CoA synthetases. Stem Cells 25:2864–2873. https://doi.org/10.1634/stemcells.2007-0308

    Article  PubMed  CAS  Google Scholar 

  41. Knobloch M, Pilz G-A, Ghesquière B, Kovacs WJ, Wegleiter T, Moore DL, Hruzova M, Zamboni N, Carmeliet P, Jessberger S (2017) A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell activity. Cell Rep 20:2144–2155. https://doi.org/10.1016/j.celrep.2017.08.029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Yki-Järvinen H (2014) Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2:901–910. https://doi.org/10.1016/s2213-8587(14)70032-4

    Article  PubMed  Google Scholar 

  43. Yang KC, Hung H-F, Lu C-W, Chang H-H, Lee L-T, Huang K-C (2016) Association of non-alcoholic fatty liver disease with metabolic syndrome independently of central obesity and insulin resistance. Sci Rep 6:27034. https://doi.org/10.1038/srep27034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Lockman KA, Baren JP, Pemberton CJ, Baghdadi H, Burgess KE, Plevris-Papaioannou N, Lee P, Howie F, Beckett G, Pryde A et al (2012) Oxidative stress rather than triglyceride accumulation is a determinant of mitochondrial dysfunction in in vitro models of hepatic cellular steatosis. Liver Int 32:1079–1092. https://doi.org/10.1111/j.1478-3231.2012.02775.x

    Article  PubMed  CAS  Google Scholar 

  45. Dufour J-F, Caussy C, Loomba R (2020) Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges. Gut 69:1877. https://doi.org/10.1136/gutjnl-2019-319104

    Article  PubMed  CAS  Google Scholar 

  46. Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, Bedossa P, Geier A, Beckebaum S, Newsome PN et al (2019) Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 394:2184–2196. https://doi.org/10.1016/S0140-6736(19)33041-7

    Article  PubMed  CAS  Google Scholar 

  47. Jalali M, Rahimlou M, Mahmoodi M, Moosavian SP, Symonds ME, Jalali R, Zare M, Imanieh MH, Stasi C (2020) The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis: An up-to date systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 159:104799. https://doi.org/10.1016/j.phrs.2020.104799

    Article  PubMed  CAS  Google Scholar 

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Funding

This research is supported by a VIDI grant (No. 91719300) from the Netherlands Organisation for Scientific Research (to Q. Pan), the Dutch Cancer Society for funding a Dutch Cancer Society Young Investigator Grant (10140) to Q. Pan, and China Scholarship Council for funding PhD fellowships to L. Wang (No.201708530248), S. Shi (No.201706230252) and R. Zhang (No.201808530490).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands

    Ling Wang, Meng Li, Bingting Yu, Jiaye Liu, Ruyi Zhang, Ibrahim Ayada, Maikel P. Peppelenbosch & Qiuwei Pan

  2. Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands

    Shaojun Shi, Monique M. A. Verstegen & Luc J. W. van der Laan

  3. Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, China

    Wanlu Cao

  4. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

    Meng Li

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  1. Ling Wang
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Contributions

Ling Wang, Meng Li, Jiaye Liu, Ruiyi Zhang, and Ibrahim Ayada performed the experimental studies. Ling Wang and Meng Li analyzed the experimental data. Bingting Yu performed the bioinformatics analysis. Luc J. W. van der Laan, Monique M. A. Verstegen, and Shaojun Shi provided the organoids lines with technical support. Maikel P. Peppelenbosch, Wanlu Cao, and Qiuwei Pan contributed to study design and supervision. The first draft of the manuscript was written by Ling Wang and all authors edited the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wanlu Cao or Qiuwei Pan.

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The experiment used of liver tissues for organoids research was approved by the Medical Ethical Council of the Erasmus MC ((MEC2006-202) and patient informed consent was given.

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The authors declare no competing interests.

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Wang, L., Li, M., Yu, B. et al. Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids. J Mol Med 100, 471–484 (2022). https://doi.org/10.1007/s00109-021-02176-x

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