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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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Autores principales: Góralska, Joanna, Raźny, Urszula, Polus, Anna, Dziewońska, Agnieszka, Gruca, Anna, Zdzienicka, Anna, Dembińska-Kieć, Aldona, Solnica, Bogdan, Micek, Agnieszka, Kapusta, Maria, Słowińska-Solnica, Krystyna, Malczewska-Malec, Małgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071278/
https://www.ncbi.nlm.nih.gov/pubmed/32069846
http://dx.doi.org/10.3390/nu12020476
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author Góralska, Joanna
Raźny, Urszula
Polus, Anna
Dziewońska, Agnieszka
Gruca, Anna
Zdzienicka, Anna
Dembińska-Kieć, Aldona
Solnica, Bogdan
Micek, Agnieszka
Kapusta, Maria
Słowińska-Solnica, Krystyna
Malczewska-Malec, Małgorzata
author_facet Góralska, Joanna
Raźny, Urszula
Polus, Anna
Dziewońska, Agnieszka
Gruca, Anna
Zdzienicka, Anna
Dembińska-Kieć, Aldona
Solnica, Bogdan
Micek, Agnieszka
Kapusta, Maria
Słowińska-Solnica, Krystyna
Malczewska-Malec, Małgorzata
author_sort Góralska, Joanna
collection PubMed
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.
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spelling pubmed-70712782020-03-19 Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis Góralska, Joanna Raźny, Urszula Polus, Anna Dziewońska, Agnieszka Gruca, Anna Zdzienicka, Anna Dembińska-Kieć, Aldona Solnica, Bogdan Micek, Agnieszka Kapusta, Maria Słowińska-Solnica, Krystyna Malczewska-Malec, Małgorzata Nutrients Article 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. MDPI 2020-02-13 /pmc/articles/PMC7071278/ /pubmed/32069846 http://dx.doi.org/10.3390/nu12020476 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Góralska, Joanna
Raźny, Urszula
Polus, Anna
Dziewońska, Agnieszka
Gruca, Anna
Zdzienicka, Anna
Dembińska-Kieć, Aldona
Solnica, Bogdan
Micek, Agnieszka
Kapusta, Maria
Słowińska-Solnica, Krystyna
Malczewska-Malec, Małgorzata
Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071278/
https://www.ncbi.nlm.nih.gov/pubmed/32069846
http://dx.doi.org/10.3390/nu12020476
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