{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:03:21Z","timestamp":1791479001499,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013500","name":"Finnish Diabetes Research Foundation","doi-asserted-by":"publisher","award":["64808"],"award-info":[{"award-number":["64808"]}],"id":[{"id":"10.13039\/501100013500","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kuopio university hospital project grant","award":["EVO\/VTR grants 2005-2019"],"award-info":[{"award-number":["EVO\/VTR grants 2005-2019"]}]},{"name":"Healh from science (TERVA)","award":["404030"],"award-info":[{"award-number":["404030"]}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["MSCA, grant no. 740264"],"award-info":[{"award-number":["MSCA, grant no. 740264"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH grant","award":["HL-095056, HL-28481, U01 DK105561"],"award-info":[{"award-number":["HL-095056, HL-28481, U01 DK105561"]}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["321716, 138006, 324494, 316458"],"award-info":[{"award-number":["321716, 138006, 324494, 316458"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERA-NET NEURON 2019 translational biomarkers","award":["334814"],"award-info":[{"award-number":["334814"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background and Aims: Gut microbiota-derived metabolites play a vital role in maintenance of human health and progression of disorders, including obesity and type 2 diabetes (T2D). Indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, has been recently shown to be lower in individuals with obesity and T2D. IPA\u2019s beneficial effect on liver health has been also explored in rodent and cell models. In this study, we investigated the association of IPA with human liver histology and transcriptomics, and the potential of IPA to reduce hepatic stellate cell activation in vitro. Methods: A total of 233 subjects (72% women; age 48.3 \u00b1 9.3 years; BMI 43.1 \u00b1 5.4 kg\/m2) undergoing bariatric surgery with detailed liver histology were included. Circulating IPA levels were measured using LC-MS and liver transcriptomics with total RNA-sequencing. LX-2 cells were used to study hepatoprotective effect of IPA in cells activated by TGF-\u03b21. Results: Circulating IPA levels were found to be lower in individuals with liver fibrosis compared to those without fibrosis (p = 0.039 for all participants; p = 0.013 for 153 individuals without T2D). Accordingly, levels of circulating IPA associated with expression of 278 liver transcripts (p &lt; 0.01) that were enriched for the genes regulating hepatic stellate cells (HSCs) activation and hepatic fibrosis signaling. Our results suggest that IPA may have hepatoprotective potential because it is able to reduce cell adhesion, cell migration and mRNA gene expression of classical markers of HSCs activation in LX-2 cells (all p &lt; 0.05). Conclusion: The association of circulating IPA with liver fibrosis and the ability of IPA to reduce activation of LX-2 cells suggests that IPA may have a therapeutic potential. Further molecular studies are needed to investigate the mechanisms how IPA can ameliorate hepatic fibrosis.<\/jats:p>","DOI":"10.3390\/nu13103509","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"3509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Ratika","family":"Sehgal","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-8865","authenticated-orcid":false,"given":"Mariana","family":"Ilha","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7423-557X","authenticated-orcid":false,"given":"Maija","family":"Vaittinen","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-576X","authenticated-orcid":false,"given":"Dorota","family":"Kaminska","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Eastern Finland and Kuopio University Hospital, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa","family":"K\u00e4rj\u00e4","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Eastern Finland and Kuopio University Hospital, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Tuomainen","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Hanhineva","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, 20500 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Pajukanta","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA"},{"name":"Institute for Precision Health, School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Pihlajam\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa D.","family":"de Mello","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The Liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. 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