Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis
Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body m...
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doaj-d60aa1612a8148cbad4381941669a7232020-11-25T02:33:37ZengMDPI AGNutrients2072-66432020-02-0112247610.3390/nu12020476nu12020476Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver SteatosisJoanna Góralska0Urszula Raźny1Anna Polus2Agnieszka Dziewońska3Anna Gruca4Anna Zdzienicka5Aldona Dembińska-Kieć6Bogdan Solnica7Agnieszka Micek8Maria Kapusta9Krystyna Słowińska-Solnica10Małgorzata Malczewska-Malec11Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandInstitute of Nursing and Midwifery, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika Str. 25, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandDepartment of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, PolandNutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25−40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01−0.32)], triglycerides [β = 0.21 (95% CI: 0.06−0.36], and FGF-21 [β = 0.20 (95%CI: 0.03−0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03−0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02−5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut−liver cross-talk.https://www.mdpi.com/2072-6643/12/2/476gipobesitymirnaliver steatosisfgf-21fgf-19cytokeratin-18gut–liver cross-talk |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joanna Góralska Urszula Raźny Anna Polus Agnieszka Dziewońska Anna Gruca Anna Zdzienicka Aldona Dembińska-Kieć Bogdan Solnica Agnieszka Micek Maria Kapusta Krystyna Słowińska-Solnica Małgorzata Malczewska-Malec |
spellingShingle |
Joanna Góralska Urszula Raźny Anna Polus Agnieszka Dziewońska Anna Gruca Anna Zdzienicka Aldona Dembińska-Kieć Bogdan Solnica Agnieszka Micek Maria Kapusta Krystyna Słowińska-Solnica Małgorzata Malczewska-Malec Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis Nutrients gip obesity mirna liver steatosis fgf-21 fgf-19 cytokeratin-18 gut–liver cross-talk |
author_facet |
Joanna Góralska Urszula Raźny Anna Polus Agnieszka Dziewońska Anna Gruca Anna Zdzienicka Aldona Dembińska-Kieć Bogdan Solnica Agnieszka Micek Maria Kapusta Krystyna Słowińska-Solnica Małgorzata Malczewska-Malec |
author_sort |
Joanna Góralska |
title |
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis |
title_short |
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis |
title_full |
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis |
title_fullStr |
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis |
title_full_unstemmed |
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis |
title_sort |
enhanced gip secretion in obesity is associated with biochemical alteration and mirna contribution to the development of liver steatosis |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2020-02-01 |
description |
Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25−40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01−0.32)], triglycerides [β = 0.21 (95% CI: 0.06−0.36], and FGF-21 [β = 0.20 (95%CI: 0.03−0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03−0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02−5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut−liver cross-talk. |
topic |
gip obesity mirna liver steatosis fgf-21 fgf-19 cytokeratin-18 gut–liver cross-talk |
url |
https://www.mdpi.com/2072-6643/12/2/476 |
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