PMID- 29235553 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 1476-5497 (Electronic) IS - 0307-0565 (Linking) VI - 42 IP - 4 DP - 2018 Apr TI - Pro-inflammatory gene expression profile in obese adults with high plasma GIP levels. PG - 826-834 LID - 10.1038/ijo.2017.305 [doi] AB - BACKGROUND: Glucose-dependent insulinotropic peptide (GIP) provides a novel link between the immune system and the gut, although results from different experimental and observational studies are contradictory, ranging from anti-inflammatory, through neutral to pro-inflammatory action of GIP. Thus, the aim of this study was to analyze inflammatory pathways on the level of gene expression and circulating inflammatory markers in relation to plasma GIP level. SUBJECTS/METHODS: The study included 128 obese adults. Two groups of obese subjects were created according to fasting GIP levels, with cutoff point at the 66th percentile and compared in respect with molecular and circulating markers of inflammation. GIP, interleukin (IL)-6 and adipokines: leptin, adiponectin, visfatin were measured by enzyme-linked immunosorbent assay. Inflammatory markers: monocyte chemoattractant protein-1 (MCP-1), sE-Selectin, sVCAM-1, sPECAM-1 were studied at fasting and after nutrient challenges. Gene expression in blood cells was determined by human gene microarray. RESULTS: Obese patients with high GIP levels had elevated fasting glucose (Q2 (Q1-Q3): 5.6 (5.0-6.0) vs 5.0 (4.8-5.4), P<0.001), homeostasis model assessment of insulin resistance (Q2 (Q1-Q3): 3.68 (2.72-5.42) vs 2.70 (2.13-4.33), P=0.021), thus increased markers of insulin resistance as well as elevated inflammatory markers Il-6 (Q2 (Q1-Q3): 1.34 (1.0-2.04) vs 1.12 (0.76-1.64), P=0.045), MCP-1 (Q2 (Q1-Q3): 363 (287-447) vs 323 (263-389), P=0.026). Leptin to adiponectin ratio was significantly associated with fasting plasma GIP levels (beta (95% CI): 0.84 (0.10-1.59)) independently of glucose levels. sE-Selectin was found to be a factor influencing GIP response to oral glucose intake (beta (95% CI): 0.47 (0.14-0.81)) and sVCAM was found to be a factor influencing GIP response to high-fat meal intake (beta (95% CI): 0.19 (0.01-0.37)). We identified 32 genes of inflammatory pathways differentially expressed in subjects with a high plasma GIP level compared to low GIP. Most upregulated genes play a role in leukocyte chemotaxis and tissue infiltration. CONCLUSIONS: These findings support the hypothesis that increased GIP signaling has a role in chronic low-grade inflammation. FAU - Goralska, J AU - Goralska J AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Razny, U AU - Razny U AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Polus, A AU - Polus A AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Stancel-Mozwillo, J AU - Stancel-Mozwillo J AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Chojnacka, M AU - Chojnacka M AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Gruca, A AU - Gruca A AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Zdzienicka, A AU - Zdzienicka A AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Dembinska-Kiec, A AU - Dembinska-Kiec A AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Kiec-Wilk, B AU - Kiec-Wilk B AD - Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland. FAU - Solnica, B AU - Solnica B AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. FAU - Malczewska-Malec, M AU - Malczewska-Malec M AD - Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171213 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Adipokines) RN - 0 (Cytokines) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Adipokines/blood/genetics/*metabolism MH - Adult MH - Cohort Studies MH - Cytokines/blood/genetics/*metabolism MH - Female MH - Gastric Inhibitory Polypeptide/*blood/genetics/*metabolism MH - Gene Expression Profiling MH - Gene Regulatory Networks MH - Humans MH - Male MH - Middle Aged MH - Obesity/*blood/epidemiology/genetics/*metabolism MH - Transcriptome/*genetics EDAT- 2017/12/14 06:00 MHDA- 2019/03/26 06:00 CRDT- 2017/12/14 06:00 PHST- 2017/02/02 00:00 [received] PHST- 2017/11/22 00:00 [revised] PHST- 2017/11/27 00:00 [accepted] PHST- 2017/12/14 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] PHST- 2017/12/14 06:00 [entrez] AID - ijo2017305 [pii] AID - 10.1038/ijo.2017.305 [doi] PST - ppublish SO - Int J Obes (Lond). 2018 Apr;42(4):826-834. doi: 10.1038/ijo.2017.305. Epub 2017 Dec 13.