Pro-inflammatory Gene Expression Profile in Obese Adults with High Plasma GIP Levels

Overview

Journal Int J Obes (Lond)

Specialty Endocrinology

Date 2017 Dec 14

PMID 29235553

Citations 11

Authors

J Goralska

U Razny

A Polus

J Stancel-Mozwillo

M Chojnacka

A Gruca

A Zdzienicka

A Dembinska-Kiec

B Kiec-Wilk

B Solnica

M Malczewska-Malec

Affiliations

Soon will be listed here.

Abstract

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 (β (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 (β (95% CI): 0.47 (0.14-0.81)) and sVCAM was found to be a factor influencing GIP response to high-fat meal intake (β (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.

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References

Choe S, Huh J, Hwang I, Kim J, Kim J . Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016; 7:30. PMC: 4829583. DOI: 10.3389/fendo.2016.00030. View

Ouchi N, Parker J, Lugus J, Walsh K . Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11(2):85-97. PMC: 3518031. DOI: 10.1038/nri2921. View

McIntosh C, Widenmaier S, Kim S . Glucose-dependent insulinotropic polypeptide signaling in pancreatic β-cells and adipocytes. J Diabetes Investig. 2014; 3(2):96-106. PMC: 4020726. DOI: 10.1111/j.2040-1124.2012.00196.x. View

Christensen M . Glucose-dependent insulinotropic polypeptide: effects on insulin and glucagon secretion in humans. Dan Med J. 2016; 63(4). View

Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H . Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002; 8(7):738-42. DOI: 10.1038/nm727. View

Veilleux A, Mayeur S, Berube J, Beaulieu J, Tremblay E, Hould F . Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis. BMC Gastroenterol. 2015; 15:119. PMC: 4574092. DOI: 10.1186/s12876-015-0342-y. View

Lee M, Yvan-Charvet L, Masters S, Murphy A . The modern interleukin-1 superfamily: Divergent roles in obesity. Semin Immunol. 2016; 28(5):441-449. DOI: 10.1016/j.smim.2016.10.001. View

Park S, Liu Z, Sui Y, Helsley R, Zhu B, Powell D . IKKβ Is Essential for Adipocyte Survival and Adaptive Adipose Remodeling in Obesity. Diabetes. 2016; 65(6):1616-29. PMC: 4878418. DOI: 10.2337/db15-1156. View

Nie Y, Ma R, Chan J, Xu H, Xu G . Glucose-dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose-dependent insulinotropic peptide receptor-overexpressing adipocytes. FASEB J. 2012; 26(6):2383-93. DOI: 10.1096/fj.11-196782. View

10.

Jalewa J, Sharma M, Holscher C . Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells. J Neurochem. 2016; 139(1):55-67. DOI: 10.1111/jnc.13736. View

11.

Kim S, Nian C, Karunakaran S, Clee S, Isales C, McIntosh C . GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis. PLoS One. 2012; 7(7):e40156. PMC: 3388996. DOI: 10.1371/journal.pone.0040156. View

12.

Gniuli D, Calcagno A, Dalla Libera L, Calvani R, Leccesi L, Caristo M . High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats. Diabetologia. 2010; 53(10):2233-40. DOI: 10.1007/s00125-010-1830-9. View

13.

Dupre J, Ross S, WATSON D, Brown J . Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973; 37(5):826-8. DOI: 10.1210/jcem-37-5-826. View

14.

Kahles F, Meyer C, Diebold S, Foldenauer A, Stohr R, Mollmann J . Glucose-dependent insulinotropic peptide secretion is induced by inflammatory stimuli in an interleukin-1-dependent manner in mice. Diabetes Obes Metab. 2016; 18(11):1147-1151. DOI: 10.1111/dom.12711. View

15.

Garcia-Martinez J, Chocarro-Calvo A, De la Vieja A, Garcia-Jimenez C . Insulin drives glucose-dependent insulinotropic peptide expression via glucose-dependent regulation of FoxO1 and LEF1/β-catenin. Biochim Biophys Acta. 2014; 1839(11):1141-50. DOI: 10.1016/j.bbagrm.2014.07.020. View

16.

Vilsboll T, Krarup T, Sonne J, Madsbad S, Volund A, Juul A . Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003; 88(6):2706-13. DOI: 10.1210/jc.2002-021873. View

17.

Li P, Deng J, Wei X, Jayasuriya C, Zhou J, Chen Q . Blockade of hypoxia-induced CXCR4 with AMD3100 inhibits production of OA-associated catabolic mediators IL-1β and MMP-13. Mol Med Rep. 2016; 14(2):1475-82. PMC: 4940083. DOI: 10.3892/mmr.2016.5419. View

18.

Meier J, Gallwitz B, Siepmann N, Holst J, Deacon C, Schmidt W . Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003; 46(6):798-801. DOI: 10.1007/s00125-003-1103-y. View

19.

Gao W, Xiong Y, Li Q, Yang H . Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics. Front Physiol. 2017; 8:508. PMC: 5516312. DOI: 10.3389/fphys.2017.00508. View

20.

Chehimi M, Robert M, El Bechwaty M, Vial G, Rieusset J, Vidal H . Adipocytes, like their progenitors, contribute to inflammation of adipose tissues through promotion of Th-17 cells and activation of monocytes, in obese subjects. Adipocyte. 2016; 5(3):275-82. PMC: 5013985. DOI: 10.1080/21623945.2015.1134402. View