{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:21:38Z","timestamp":1778160098490,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["20252BAC200579"],"award-info":[{"award-number":["20252BAC200579"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["PY-2025001B"],"award-info":[{"award-number":["PY-2025001B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The dysregulation of intestinal lipid metabolism induced by a high-fat diet (HFD) is associated with metabolic diseases; however, the validity of intestinal organoids (IOs) as substitutes for traditional research systems remains uncertain. This study aimed to determine whether fatty acid (FA)-treated IOs accurately replicate intestinal lipid metabolism observed in HFD mice. Male C57BL\/6 mice were fed either a normal chow diet (NCD) or HFD for 12 weeks, while mouse small intestinal crypt-derived IOs were treated in vitro with either an FA cocktail or a vehicle. Mice on the HFD exhibited phenotypes characteristic of metabolic syndrome, including intestinal lipid accumulation, upregulation of lipid catabolic genes, and downregulation of lipogenic genes. FA-treated IOs demonstrated enhanced budding frequency, lipid droplet accumulation, enriched lipid catabolism pathways, and suppressed lipogenesis, aligning with the in vivo findings. Omics analyses of the top 87 variable genes indicated a strong congruence between FA-treated IOs and intestinal tissues from HFD mice, with control groups clustering distinctly. The differentially expressed genes in both models were implicated in metabolic reprogramming, immune modulation, and barrier remodeling. Therefore, FA-treated IOs recapitulate key morphological and transcriptional characteristics of intestinal lipid metabolism in HFD mice, offering a valuable complementary model for investigating intestinal metabolic disorders.<\/jats:p>","DOI":"10.3390\/biom16050688","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adult Stem Cell-Derived Intestinal Organoids as In Vitro Models of High-Fat Diet-Related Intestinal Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Yinju","family":"Liu","sequence":"first","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM (2024SSY07102), Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanying","family":"Chen","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM (2024SSY07102), Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengcai","family":"Liu","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM (2024SSY07102), Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Jia","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM (2024SSY07102), Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlong","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM (2024SSY07102), Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-4272","authenticated-orcid":false,"given":"Jinlong","family":"Tan","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China"},{"name":"Jiangxi Health Industry Institute of Traditional Chinese Medicine, Nanchang 330115, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pavlidou, E., Papadopoulou, S.K., Fasoulas, A., Papaliagkas, V., Alexatou, O., Chatzidimitriou, M., Mentzelou, M., and Giaginis, C. (2023). Diabesity and Dietary Interventions: Evaluating the Impact of Mediterranean Diet and Other Types of Diets on Obesity and Type 2 Diabetes Management. Nutrients, 16.","DOI":"10.3390\/nu16010034"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1002\/imt2.69","article-title":"New insights into the mechanisms of high-fat diet mediated gut microbiota in chronic diseases","volume":"2","author":"Chen","year":"2023","journal-title":"Imeta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4014\/jmb.2312.12031","article-title":"Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome","volume":"34","author":"Chae","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.semcancer.2020.10.003","article-title":"Dietary fat, bile acid metabolism and colorectal cancer","volume":"73","author":"Ocvirk","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Malesza, I.J., Malesza, M., Walkowiak, J., Mussin, N., Walkowiak, D., Aringazina, R., Bartkowiak-Wieczorek, J., and M\u0105dry, E. (2021). High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells, 10.","DOI":"10.3390\/cells10113164"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1017\/S0954422410000168","article-title":"High-fat diet-induced obesity in animal models","volume":"23","author":"Hariri","year":"2010","journal-title":"Nutr. Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prabhu, G.S., Rao Kg, M., Concessao, P.L., and Rai, K.S. (2025). Role of High-Fat Diet Alone on Lipids, Arterial Wall and Hippocampal Neural Cell Alterations in Animal Models and Their Implications for Humans. Biology, 14.","DOI":"10.3390\/biology14080971"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106135","DOI":"10.1016\/j.neubiorev.2025.106135","article-title":"Behavioural and physiological effects of binge eating: A systematic review and meta-analysis of animal models","volume":"173","author":"Rehn","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1097\/HEP.0000000000000343","article-title":"Human liver organoids: From generation to applications","volume":"79","author":"Afonso","year":"2024","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1177\/00236772221145647","article-title":"The human skin organ culture model as an optimal complementary tool for murine pemphigus models","volume":"57","author":"Hartmann","year":"2023","journal-title":"Lab. Anim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.aninu.2024.01.006","article-title":"Development and application of a multi-step porcine in vitro system to evaluate feedstuffs and feed additives for their efficacy in nutrient digestion, digesta characteristics, and intestinal immune responses","volume":"17","author":"Kim","year":"2024","journal-title":"Anim. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lechuga, S., Braga-Neto, M.B., Naydenov, N.G., Rieder, F., and Ivanov, A.I. (2023). Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1108289"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41392-022-01024-9","article-title":"Human organoids in basic research and clinical applications","volume":"7","author":"Tang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.semcdb.2022.10.001","article-title":"Microfluidic organoids-on-a-chip: The future of human models","volume":"144","author":"Saorin","year":"2023","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_16","first-page":"40","article-title":"Bioengineered skin organoids: From development to applications","volume":"10","author":"Hong","year":"2023","journal-title":"Mil. Med. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41420-023-01556-1","article-title":"Stem cell-derived intestinal organoids: A novel modality for IBD","volume":"9","author":"Tian","year":"2023","journal-title":"Cell. Death Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101049","DOI":"10.1016\/j.plipres.2020.101049","article-title":"The memory of the fatty acid system","volume":"79","author":"Straub","year":"2020","journal-title":"Prog. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101712","DOI":"10.1016\/j.gendis.2025.101712","article-title":"Emerging roles and therapeutic implications of lipid droplet protein perilipin 2 in liver disease","volume":"13","author":"Xiang","year":"2026","journal-title":"Genes. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1053\/j.gastro.2023.07.017","article-title":"Ceramides Increase Fatty Acid Utilization in Intestinal Progenitors to Enhance Stemness and Increase Tumor Risk","volume":"165","author":"Li","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e20201606","DOI":"10.1084\/jem.20201606","article-title":"Lipid metabolism and cancer","volume":"218","author":"Bian","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.ajcnut.2024.12.026","article-title":"The relationship between a high-fat diet, gut microbiome, and systemic chronic inflammation: Insights from integrated multiomics analysis","volume":"121","author":"Du","year":"2025","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/advances\/nmz061","article-title":"Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review","volume":"11","author":"Rohr","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13287-023-03521-2","article-title":"Vascular organoids: Unveiling advantages, applications, challenges, and disease modelling strategies","volume":"14","author":"Cornelius","year":"2023","journal-title":"Stem Cell. Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41586-018-0858-8","article-title":"Human blood vessel organoids as a model of diabetic vasculopathy","volume":"565","author":"Wimmer","year":"2019","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1053\/j.gastro.2020.06.010","article-title":"Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease","volume":"159","author":"Ramli","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tu, C., Cunningham, N.J., Zhang, M., and Wu, J.C. (2021). Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.613837"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"eadu4172","DOI":"10.1126\/sciadv.adu4172","article-title":"MAIT cell homing in intestinal homeostasis and inflammation","volume":"11","author":"Wu","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41586-021-03312-w","article-title":"SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801","volume":"591","author":"Wahl","year":"2021","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Purev, E., Bahmed, K., and Kosmider, B. (2024). Alveolar Organoids in Lung Disease Modeling. Biomolecules, 14.","DOI":"10.3390\/biom14010115"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.euf.2024.08.008","article-title":"Patient-derived Organoids in Bladder Cancer: Opportunities and Challenges","volume":"11","author":"Egger","year":"2025","journal-title":"Eur. Urol. Focus."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.7150\/ijbs.114373","article-title":"Cancer patient-derived organoids: Novel models for the study of natural products","volume":"21","author":"Liu","year":"2025","journal-title":"Int. J. Biol. Sci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/688\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:06:30Z","timestamp":1778159190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050688"],"URL":"https:\/\/doi.org\/10.3390\/biom16050688","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]}}}