Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Filters applied. Clear all
. 2020 Feb 13;12(2):476.
doi: 10.3390/nu12020476.

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

Affiliations
Free PMC article

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

Joanna Góralska et al. Nutrients. .
Free PMC article

Abstract

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.

Keywords: FGF-19; FGF-21; GIP; cytokeratin-18; gut–liver cross-talk; liver steatosis; miRNA; obesity.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Fatty liver risk markers: ALT (a), GGT (b), FLI (c), cytokeratin-18 (d), FGF-19 (e), and FGF-21 (f) in the Low GIP (n = 85) and High GIP (n = 43) groups of patients. Values are presented as median (line), upper and lower quartile (box), and minimum and maximum (whiskers). Significant differences are indicated as * p < 0.05 (Mann–Whitney U test, Statistica softaware v.13). Abbreviations: High GIP—group of subjects with fasting plasma GIP level >66th percentile, Low GIP—group of subjects with plasma fasting GIP level ≤66th, ALT—alanine aminotransferase, GGT—gamma-glutamyltransferase, FGF-19—fibroblast growth factor-19, FGF-21—fibroblast growth factor-21.
Figure 2
Figure 2
Volcano plot shows the relative expression of microRNAs in the high GIP versus low GIP group; fold change boundary: 1.2, p-value boundary: 0.05 (prepared using DataAssist Software v.3.01).
Figure 3
Figure 3
Quantitative PCR (TaqMan low density array (TLDA)) showing the expression of microRNAs in the high GIP versus low GIP group. Relative miRNA levels are expressed as fold of change, with U6 snRNA used as endogenous control; upregulated miRNA—black bars, downregulated miRNA—gray bars (n = 18; p < 0.05; t-test, DataAssist Software v.3.01).
Figure 4
Figure 4
Interactions of microRNAs with gene pathways. The known miRNA gene targets were extracted using the mirPath v.3 DIANA TOOLS. The miRNA-gene interaction network was generated through Cytoscape with ClueGO.

Similar articles

See all similar articles

References

    1. Pederson R.A., Schubert H.E., Brown J.C. The insulinotropic action of gastric inhibitory polypeptide. Can. J. Physiol. Pharmacol. 1975;53:217–223. doi: 10.1139/y75-032. - DOI - PubMed
    1. Pfeiffer A.F.H., Keyhani-Nejad F. High Glycemic Index Metabolic Damage—A Pivotal Role of GIP and GLP-1. Trends Endocrinol. Metab. 2018;29:289–299. doi: 10.1016/j.tem.2018.03.003. - DOI - PubMed
    1. Musso G., Gambino R., Pacini G., De Michieli F., Cassader M. Prolonged saturated fat–induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: Dysregulated enteroadipocyte axis as a novel feature of fatty liver. Am. J. Clin. Nutr. 2009;89:558–567. doi: 10.3945/ajcn.2008.26720. - DOI - PubMed
    1. Tseng C.C., Jarboe L.A., Wolfe M.M. Regulation of glucose-dependent insulinotropic peptide gene expression by a glucose meal. Am. J. Physiol. Liver Physiol. 1994;266:G887–G891. doi: 10.1152/ajpgi.1994.266.5.G887. - DOI - PubMed
    1. Bailey C.J., Flatt P.R., Kwasowski P., Powell C.J., Marks V. Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets. Acta Endocrinol. 1986;112:224–229. doi: 10.1530/acta.0.1120224. - DOI - PubMed
Feedback