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Open AccessArticle

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

1
Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, Poland
2
Institute of Nursing and Midwifery, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika Str. 25, 31-501 Krakow, Poland
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(2), 476; https://doi.org/10.3390/nu12020476
Received: 14 January 2020 / Revised: 3 February 2020 / Accepted: 6 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Nutrition, microRNAs and Human Health)
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. View Full-Text
Keywords: GIP; obesity; miRNA; liver steatosis; FGF-21; FGF-19; cytokeratin-18; gut–liver cross-talk GIP; obesity; miRNA; liver steatosis; FGF-21; FGF-19; cytokeratin-18; gut–liver cross-talk
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Góralska, J.; Raźny, U.; Polus, A.; Dziewońska, A.; Gruca, A.; Zdzienicka, A.; Dembińska-Kieć, A.; Solnica, B.; Micek, A.; Kapusta, M.; Słowińska-Solnica, K.; Malczewska-Malec, M. Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis. Nutrients 2020, 12, 476.

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