biostudies-literatureIlha MGenomMed Doctoral ProgrammeJane and Aatos Erkko FoundationNovo Nordisk FoundationHealth from ScienceUniversity of HelsinkiNational Institutes of Health (NIH)Helsinki University HospitalNHLBI NIH HHSGovernment Research FundsFinnish Diabetes Research FoundationRegion SkåneFinnish Medical FoundationSwedish Research CouncilNational Institutes of HealthAcademy of FinlandSwedish Foundation for the Strategic ResearchEFSDEXODIABNIDDK NIH HHSThe Swedish Diabetes FoundationNHGRI NIH HHSGyllenberg FoundationHorizon 2020 Framework Programme of the European UnionKuopio University Hospital253https://www.ebi.ac.uk/biostudies/studies/S-EPMC11871697biostudies-literatureUnknown23(1)<h4>Background & aims</h4>We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored the transcriptome and DNA methylome associated with serum IPA levels in human liver from obese individuals together with IPA effects on shifting the hepatic stellate cell (HSC) phenotype to inactivation in vitro.<h4>Methods</h4>A total of 116 obese individuals without type 2 diabetes (T2D) (age 46.8 ± 9.3 years; BMI: 42.7 ± 5.0 kg/m²) from the Kuopio OBesity Surgery (KOBS) study undergoing bariatric surgery were included. Circulating IPA levels were measured using LC-MS, liver transcriptomics with total RNA-sequencing and DNA methylation with Infinium HumanMethylation450 BeadCJournal of translational medicineIndole-3-propionic acid promotes hepatic stellate cells inactivation.PMC11871697314383336449R01HL170604335443740264335444R01 DK132775272376NNF20OC0060547337120266286324494R01HG010505EVO/VTR grants 2005–2019138006314455314456316458404030335445Dnr IRC15-0067314454R01 HL170604335446R01 HG010505NNF10OC1013354EVO/VTR grants 2005-2019NNF17OC0027232R01DK132775Pietilainen KHPirinen EMatilainen JVirtanen KAMannisto VRilla KSehgal RVaittinen MPajukanta PKaminska DGandhi SLing CPihlajamaki JRomeo SIlha MfalseIndole-3-propionic acid promotes hepatic stellate cells inactivation.<h4>Background & aims</h4>We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored the transcriptome and DNA methylome associated with serum IPA levels in human liver from obese individuals together with IPA effects on shifting the hepatic stellate cell (HSC) phenotype to inactivation in vitro.<h4>Methods</h4>A total of 116 obese individuals without type 2 diabetes (T2D) (age 46.8 ± 9.3 years; BMI: 42.7 ± 5.0 kg/m²) from the Kuopio OBesity Surgery (KOBS) study undergoing bariatric surgery were included. Circulating IPA levels were measured using LC-MS, liver transcriptomics with total RNA-sequencing and DNA methylation with Infinium HumanMethylation450 BeadC2025-01-01T00:00:00Z2025 Mar2026-06-02T20:08:32.895Z2025-04-07T07:53:30.514ZS-EPMC118716974002553010.1186/s12967-025-06266-z