Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kopernika Str. 15A, 31-501 Krakow, Poland.
Institute of Nursing and Midwifery, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika Str. 25, 31-501 Krakow, Poland.
Nutrients. 2020 Feb 13;12(2):476. doi: 10.3390/nu12020476.
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.
营养过剩会增强葡萄糖依赖性胰岛素释放多肽（GIP）的分泌，而这反过来可能导致肝脂肪变性的发生。我们假设肥胖症患者中升高的 GIP 水平可能会通过 microRNAs 影响肝损伤标志物。这项研究涉及 128 名受试者（体重指数（BMI）为 25-40）。检测了空腹和餐后的 GIP、血糖、胰岛素和脂质，以及空腹丙氨酸氨基转移酶（ALT）、γ-谷氨酰转移酶（GGT）、细胞角蛋白 18、成纤维细胞生长因子（FGF）-19 和 FGF-21。使用 TaqMan 低密度阵列对血液 microRNAs 进行定量分析。空腹 GIP 与 ALT [β=0.16（置信区间（CI）：0.01-0.32）]、甘油三酯 [β=0.21（95%CI：0.06-0.36）] 和 FGF-21 [β=0.20（95%CI：0.03-0.37）]呈正相关；而餐后 GIP 与 GGT [β=0.17（95%CI：0.03-0.32）]呈正相关。高 GIP 组与低 GIP 组相比，升高的脂肪肝指数（>73%）的比值比为 2.42（95%CI：1.02-5.72）。与高 GIP 血浆水平相关的 miRNA 谱包括上调的 miR-136-5p、miR-320a、miR-483-5p、miR-520d-5p、miR-520b、miR-30e-3p 和 miR-571。对这些 microRNAs 与基因表达途径的相互作用进行分析表明，它们可能有助于调节与胰岛素抵抗、脂肪酸代谢和脂肪细胞因子信号相关的基因的活性。肥胖症中空腹和餐后 GIP 的过度分泌与肝损伤标志物以及 FGF-21 血浆水平的升高有关。差异表达的 microRNAs 表明，还有其他表观遗传因素参与了肠道-肝脏的相互作用。
