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Hepatic insulin res...
Hepatic insulin resistance is the basis of bile acid dysmetabolism in non-alcoholic fatty liver disease
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- Qadri, Sami (author)
- University of Helsinki and Helsinki University Hospital, Department of Medicine, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Vartiainen, Emilia (author)
- University of Helsinki, Institute for Molecular Medicine Finland, FIMM, Helsinki, Finland
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- Ahlholm, Noora (author)
- University of Helsinki and Helsinki University Hospital, Department of Medicine, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Porthan, Kimmo (author)
- University of Helsinki and Helsinki University Hospital, Department of Medicine, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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- Juuti, Anne (author)
- University of Helsinki and Helsinki University Hospital, Department of Gastrointestinal Surgery, Abdominal Center, Helsinki, Finland
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- Sammalkorpi, Henna (author)
- University of Helsinki and Helsinki University Hospital, Department of Gastrointestinal Surgery, Abdominal Center, Helsinki, Finland
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- Penttilä, Anne (author)
- University of Helsinki and Helsinki University Hospital, Department of Gastrointestinal Surgery, Abdominal Center, Helsinki, Finland
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- Arola, Johanna (author)
- University of Helsinki and Helsinki University Hospital, Department of Pathology, Helsinki, Finland
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- Tukiainen, Taru (author)
- University of Helsinki, Institute for Molecular Medicine Finland, FIMM, Helsinki, Finland
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- Oresic, Matej, 1967- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,University of Turku and Åbo Akademi University, Turku Bioscience Centre, Turku, Finland
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- Hyötyläinen, Tuulia, 1971- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- Yki-Järvinen, Hannele (author)
- University of Helsinki and Helsinki University Hospital, Department of Medicine, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 77:Suppl. 1, s. S694-S695
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Background and aims: Non-alcoholic fatty liver disease (NAFLD) is associated with increased circulating bile acids (BAs). It is unknown whether this reflects altered intrahepatic BA metabolism due to NAFLD or the associated insulin resistance (IR). To dissociate steatosis from IR, we compared BA metabolism in NAFLD associated with either IR or high genetic risk.Method: In 106 patients undergoing a liver biopsy, we analysed serum/liver BAs, the hepatic transcriptome (RNA-seq), and concentrations of plasma FGF-19 (marker of intestinal BA metabolism). Using HOMA-IR and a validated weighted Polygenic Risk Score (PRS) for NAFLD, we divided the patients into matched groups to compare the effects of NAFLD associated with IR (‘High HOMA-IR’ vs. ‘LowHOMA-IR’) or with high genetic risk (‘High PRS’ vs. ‘Low PRS’) on BA metabolism.Results: An untargeted analysis identified distinct clusters of patients with simultaneously increased BAs, HOMA-IR, and liver fat content. Compared to ‘Low HOMA-IR’, patients with ‘High HOMA-IR’ had significantly higher total (+57%, P = 0.011) and especially conjugated (+82%, P = 0.002) serum BAs, but unchanged hepatic BAs. Expression of the primary hepatic BA uptake transporter NTCP was down-regulated, while plasma FGF-19 was unchanged. Despite having the same degree of steatosis and NASH compared to the ‘High HOMA-IR’ group, patients with ‘High PRS’ had similar serum/liver BAs compared to those with ‘Low PRS’. Stage F3-F4 liver fibrosis independently predicted higher serum BAs.Conclusion: In NAFLD without advanced fibrosis, serum BAs are increased due to IR, which may impair hepatocellular BA uptake. Intrahepatic BAs are unchanged in NAFLD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
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- vet (subject category)
- art (subject category)
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- By the author/editor
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Qadri, Sami
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Vartiainen, Emil ...
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Ahlholm, Noora
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Porthan, Kimmo
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Juuti, Anne
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Sammalkorpi, Hen ...
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Penttilä, Anne
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Arola, Johanna
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Tukiainen, Taru
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Oresic, Matej, 1 ...
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Hyötyläinen, Tuu ...
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Yki-Järvinen, Ha ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
- Articles in the publication
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Journal of Hepat ...
- By the university
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Örebro University