Skip to main content
SpringerLink
Log in

Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes

  • Research
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The corresponding authors will make the data presented in this study available upon request.

References

  1. Zimmet P, Alberti KG, Magliano DJ, Bennett PH (2016) Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat Rev Endocrinol 12(10):616–622. https://doi.org/10.1038/nrendo.2016.105

    Article  PubMed  Google Scholar 

  2. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddigi H, Uribe KB, Ostolaza H, Martín C (2020) Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci 21(17):6275. https://doi.org/10.3390/ijms21176275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hayden MR (2023) Overview and new insights into the metabolic syndrome: risk factors and emerging variables in the development of type 2 diabetes and cerebrocardiovascular disease. Medicina (Kaunas) 9(3):561. https://doi.org/10.3390/medicina59030561

    Article  Google Scholar 

  4. Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148(5):852–871. https://doi.org/10.1016/j.cell.2012.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maury E, Brichard SM (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314(1):1–16. https://doi.org/10.1016/j.mce.2009.07.031

    Article  CAS  PubMed  Google Scholar 

  6. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445. https://doi.org/10.1146/annurev-immunol-031210-101322

    Article  CAS  PubMed  Google Scholar 

  7. Sell H, Eckel J (2010) Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes. Curr Opin Clin Nutr Metab Care 13(4):366–370. https://doi.org/10.1097/MCO.0b013e32833aab7f

    Article  PubMed  Google Scholar 

  8. Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NMJ, Magness S, Jobin C, Lund PK (2010) High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5(8):e12191. https://doi.org/10.1371/journal.pone.0012191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Luck H, Tsai S, Chung J, Clemente-Casares X, Ghazarian M, Revelo XS, Lei H, Luk CT, Shi SY, Surendra A, Copeland JK, Ahn J, Prescott D, Rasmussen BA, Chng MH, Engleman EG, Girardin SE, Lam TK, Croitoru K, Dunn S, Philpott DJ, Guttman DS, Woo M, Winer S, Winer DA (2015) Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab 21(4):527–542. https://doi.org/10.1016/j.cmet.2015.03.001

    Article  CAS  PubMed  Google Scholar 

  10. Nezami BG, Mwangi SM, Lee JE, Jeppsson S, Anitha M, Yarandi SS, Farris AB 3rd, Srinivasan S (2014) MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice. Gastroenterology 146(2):473–83.e3. https://doi.org/10.1053/j.gastro.2013.10.053

    Article  CAS  PubMed  Google Scholar 

  11. Anitha M, Reichardt F, Tabatabavakili S, Nezami BG, Chassaing B, Mwangi S, Vijay-Kumar M, Gewirtz A, Srinivasan S (2016) Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice. Cell Mol Gastroenterol Hepatol 2(3):328–339. https://doi.org/10.1016/j.jcmgh.2015.12.008

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhao M, Liao D, Zhao J (2017) Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 8(6):249–269. https://doi.org/10.4239/wjd.v8.i6.249

    Article  PubMed  PubMed Central  Google Scholar 

  13. Le Pluart D, Sabaté JM, Bouchoucha M, Hercberg S, Benamouzig R, Julia C (2015) Functional gastrointestinal disorders in 35,447 adults and their association with body mass index. Aliment Pharmacol Ther 41(8):758–767. https://doi.org/10.1111/apt.13143

    Article  PubMed  Google Scholar 

  14. Jung HK, Kim DY, Moon IH, Hong YS (2003) Colonic transit time in diabetic patients comparison with healthy subjects and the effect of autonomic neuropathy. Yonsei Med J 44(2):265–272. https://doi.org/10.3349/ymj.2003.44.2.265

    Article  PubMed  Google Scholar 

  15. Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M (2001) Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med 161(16):1989–1996. https://doi.org/10.1001/archinte.161.16.1989

    Article  CAS  PubMed  Google Scholar 

  16. Beraldi EJ, Soares A, Borges SC, de Souza AC, Natali MR, Bazotte RB, Buttow NC (2015) High-fat diet promotes neuronal loss in the myenteric plexus of the large intestine in mice. Dig Dis Sci 60(4):841–849. https://doi.org/10.1007/s10620-014-3402-1

    Article  CAS  PubMed  Google Scholar 

  17. GalicBeraldi EJ, Borges SC, de Almeida FLA, Dos Santos A, Saad MJA, Buttow NC (2020) Colonic neuronal loss and delayed motility induced by high-fat diet occur independently of changes in the major groups of microbiota in Swiss mice. Neurogastroenterol Motil 32(2):e13745. https://doi.org/10.1111/nmo.13745

    Article  Google Scholar 

  18. Burnstock G (2014) Purinergic signaling in the gastrointestinal tract and related organs in health and disease. Purinergic Signal 10(1):3–50. https://doi.org/10.1007/s11302-013-9397-9

    Article  CAS  PubMed  Google Scholar 

  19. Lazarowski ER (2012) Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal 8(3):359–373. https://doi.org/10.1007/s11302-012-9304-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dosch M, Gerber J, Jebbawi F, Beldi G (2018) Mechanisms of ATP release by inflammatory cells. Int J Mol Sci 19(4):1222. https://doi.org/10.3390/ijms19041222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vuerich M, Mukherjee S, Robson SC, Longhi MS (2020) Control of gut inflammation by modulation of purinergic signaling. Front Immunol 11:1882. https://doi.org/10.3389/fimmu.2020.01882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Eltzschig HK, Sitkovsky MV, Robson SC (2012) Purinergic signaling during inflammation. N Engl J Med 367(24):2322–2333. https://doi.org/10.1056/NEJMra1205750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Longhi MS, Moss A, Jiang ZG, Robson SC (2017) Purinergic signaling during intestinal inflammation. J Mol Med (Berl) 95(9):915–925. https://doi.org/10.1007/s00109-017-1545-1

    Article  CAS  PubMed  Google Scholar 

  24. Cardenas-Perez RE, Fuentes-Mera L, de la Garza AL, Torre-Villalvazo I, Reyes-Castro LA, Rodriguez-Rocha H, Garcia-Garcia A, Corona-Castillo JC, Tovar AR, Zambrano E, Ortiz-Lopez R, Saville J, Fuller M, Camacho A (2018) Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring. Nutr Metab (Lond) 15:38. https://doi.org/10.1186/s12986-018-0279-6

    Article  CAS  PubMed  Google Scholar 

  25. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM (2000) A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49(11):1390–1394. https://doi.org/10.1053/meta.2000.17721

    Article  CAS  PubMed  Google Scholar 

  26. Virtue S, Vidal-Puig A (2021) GTTs and ITTs in mice: simple tests, complex answers. Nat Metab 3(7):883–886. https://doi.org/10.1038/s42255-021-00414-7

    Article  PubMed  Google Scholar 

  27. Monzillo LU, Hamdy O (2003) Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 61(12):397–412. https://doi.org/10.1301/nr2003.dec.397-412

    Article  PubMed  Google Scholar 

  28. Tan P, Pepin É, Lavoie JL (2018) Mouse adipose tissue collection and processing for RNA analysis. J Vis Exp 131:57026. https://doi.org/10.3791/57026

    Article  Google Scholar 

  29. Perruzza L, Gargari G, Proietti M, Fosso B, D’Erchia AM, Faliti CE, Rezzonico-Jost T, Scribano D, Mauri L, Colombo D, Pellegrini G, Moregola A, Mooser C, Pesole G, Nicoletti M, Norata GD, Geuking MB, McCoy KD, Guglielmetti S, Grassi F (2017) T Follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP. Cell Rep 18(11):2566–2575. https://doi.org/10.1016/j.celrep.2017.02.061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yu T, Sungelo MJ, Goldberg IJ, Wang H, Eckel RH (2017) Streptozotocin-treated high fat fed mice: a new type 2 diabetes model used to study canagliflozin-induced alterations in lipids and lipoproteins. Horm Metab Res 49(5):400–406. https://doi.org/10.1055/s-0042-110934

    Article  CAS  PubMed  Google Scholar 

  31. Kanasaki K, Koya D (2011) Biology of obesity: lessons from animal models of obesity. J Biomed Biotechnol 2011:197636. https://doi.org/10.1155/2011/197636

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kawai T, Autieri MV, Scalia R (2021) Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol 320(3):C375–C391. https://doi.org/10.1152/ajpcell.00379.2020

    Article  CAS  PubMed  Google Scholar 

  33. Moraes RC, Blondet A, Birkenkamp-Demtroeder K, Tirard J, Orntoft TF, Gertler A, Durand P, Naville D, Bégeot M (2003) Study of the alteration of gene expression in adipose tissue of diet-induced obese mice by microarray and reverse transcription-polymerase chain reaction analyses. Endocrinology 144(11):4773–4782. https://doi.org/10.1210/en.2003-0456

    Article  CAS  PubMed  Google Scholar 

  34. Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D (2007) Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 148(10):4687–4694. https://doi.org/10.1210/en.2007-0175

    Article  CAS  PubMed  Google Scholar 

  35. Huber J, Kiefer FW, Zeyda M, Ludvik B, Silberhumer GR, Prager G, Zlabinger GJ, Stulnig TM (2008) CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab 93(8):3215–21. https://doi.org/10.1210/jc.2007-2630

    Article  CAS  PubMed  Google Scholar 

  36. Zietz B, Büchler C, Herfarth H, Müller-Ladner U, Spiegel D, Schölmerich J, Schäffler A (2005) Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A–>G promoter polymorphism. Diabetes Obes Metab 7(5):570–578. https://doi.org/10.1111/j.1463-1326.2004.00436.x

    Article  CAS  PubMed  Google Scholar 

  37. Lee CH, Lam KS (2019) Obesity-induced insulin resistance and macrophage infiltration of the adipose tissue: a vicious cycle. J Diabetes Investig 10(1):29–31. https://doi.org/10.1111/jdi.12918

    Article  PubMed  Google Scholar 

  38. Rourke JL, Dranse HJ, Sinal CJ (2013) Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes Rev 14(3):245–262. https://doi.org/10.1111/obr.12009

    Article  CAS  PubMed  Google Scholar 

  39. Neuparth MJ, Proença JB, Santos-Silva A, Coimbra S (2013) Adipokines, oxidized low-density lipoprotein, and C-reactive protein levels in lean, overweight, and obese portuguese patients with type 2 diabetes. ISRN Obes 2013:142097. https://doi.org/10.1155/2013/142097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ernst MC, Issa M, Goralski KB, Sinal CJ (2010) Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology 151(5):1998–2007. https://doi.org/10.1210/en.2009-1098

    Article  CAS  PubMed  Google Scholar 

  41. Kurashima IJ, Malesza M, Walkowiak J, Mussin N, Walkowiak D, Aringazina R, Bartkowiak-Wieczorek J, Mądry E (2021) High-fat, Western-style diet, systemic inflammation, and gut microbiota: a narrative review. Cells 10(11):3164. https://doi.org/10.3390/cells10113164

    Article  CAS  Google Scholar 

  42. Xie Y, Ding F, Di W, Lv Y, Xia F, Sheng Y, Yu J, Ding G (2020) Impact of a high-fat diet on intestinal stem cells and epithelial barrier function in middle-aged female mice. Mol Med Rep 21(3):1133–1144. https://doi.org/10.3892/mmr.2020.10932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kim JE, Seol A, Choi YJ, Lee SJ, Jin YJ, Roh YJ, Song HJ, Hong JT, Hwang DY (2022) Similarities and differences in constipation phenotypes between Lep knockout mice and high fat diet-induced obesity mice. PLoS One 17(12):e0276445. https://doi.org/10.1371/journal.pone.0276445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chen P, Zhao J, Zhang H, Yang X, Zhao T, Zhang H, Yan M, Pan L, Li X, Zhang Y, Li P (2017) Tangshen formula attenuates colonic structure remodeling in type 2 diabetic rats. Evid Based Complement Alternat Med 2017:4064156. https://doi.org/10.1155/2017/4064156.S

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ding S, Lund PK (2011) Role of intestinal inflammation as an early event in obesity and insulin resistance. Curr Opin Clin Nutr Metab Care 14(4):328–333. https://doi.org/10.1097/MCO.0b013e3283478727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7(10):e47713. https://doi.org/10.1371/journal.pone.0047713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fuster JJ, Walsh K (2014) The good, the bad, and the ugly of interleukin-6 signaling. EMBO J 33(13):1425–1427. https://doi.org/10.15252/embj.201488856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zigmond E, Bernshtein B, Friedlander G, Walker CR, Yona S, Kim KW, Brenner O, Krauthgamer R, Varol C, Müller W, Jung S (2014) Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40(5):720–733. https://doi.org/10.1016/j.immuni.2014.03.012

    Article  CAS  PubMed  Google Scholar 

  49. Shouval DS, Biswas A, Goettel JA, McCann K, Conaway E, Redhu NS, Mascanfroni ID, Al Adham Z, Lavoie S, Ibourk M, Nguyen DD, Samsom JN, Escher JC, Somech R, Weiss B, Beier R, Conklin LS, Ebens CL, Santos FG, Ferreira AR, Sherlock M, Bhan AK, Müller W, Mora JR, Quintana FJ, Klein C, Muise AM, Horwitz BH, Snapper SB (2014) Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity 40(5):706–719. https://doi.org/10.1016/j.immuni.2014.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Inami A, Kiyono H, Kurashima Y (2018) ATP as a pathophysiologic mediator of bacteria-host crosstalk in the gastrointestinal tract. Int J Mol Sci 19(8):2371. https://doi.org/10.3390/ijms19082371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Burnstock G, Di Virgilio F (2013) Purinergic signaling and cancer. Purinergic Signal 9(4):491–540. https://doi.org/10.1007/s11302-013-9372-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Antonioli L, Colucci R, Pellegrini C, Giustarini G, Tuccori M, Blandizzi C, Fornai M (2013) The role of purinergic pathways in the pathophysiology of gut diseases: pharmacological modulation and potential therapeutic applications. Pharmacol Ther 139(2):157–188. https://doi.org/10.1016/j.pharmthera.2013.04.002

    Article  CAS  PubMed  Google Scholar 

  53. D’Antongiovanni V, Benvenuti L, Fornai M, Pellegrini C, van den Wijngaard R, Cerantola S, Giron MC, Caputi V, Colucci R, Haskó G, Németh ZH, Blandizzi C, Antonioli L (2020) Glial A2B adenosine receptors modulate abnormal tachykininergic responses and prevent enteric inflammation associated with high fat diet-induced obesity. Cells 9(5):1245. https://doi.org/10.3390/cells9051245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Huang S, Apasov S, Koshiba M, Sitkovsky M (1997) Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90(4):1600–1610

    Article  CAS  PubMed  Google Scholar 

  55. Robson SC, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2(2):409–430. https://doi.org/10.1007/s11302-006-9003-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Antonioli L, Pacher P, Vizi ES, Haskó G (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med 19(6):355–367. https://doi.org/10.1016/j.molmed.2013.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang R, Wang Y, Wu C, Jin G, Zhu F, Yang Y, Wang Y, Zhou G (2023) CD73 blockade alleviates intestinal inflammatory responses by regulating macrophage differentiation in ulcerative colitis. Exp Ther Med 25(6):272. https://doi.org/10.3892/etm.2023.11972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Antonioli L, Fornai M, Pellegrini C, Bertani L, Nemeth ZH, Blandizzi C (2020) Inflammatory bowel diseases: it’s time for the adenosine system. Front Immunol 11:1310. https://doi.org/10.3389/fimmu.2020.01310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K, Takeda K (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808–812. https://doi.org/10.1038/nature07240

    Article  CAS  PubMed  Google Scholar 

  60. Neves AR, Castelo-Branco MT, Figliuolo VR, Bernardazzi C, Buongusto F, Yoshimoto A, Nanini HF, Coutinho CM, Carneiro AJ, Coutinho-Silva R, de Souza HS (2014) Overexpression of ATP-activated P2X7 receptors in the intestinal mucosa is implicated in the pathogenesis of Crohn’s disease. Inflamm Bowel Dis 20(3):444–457. https://doi.org/10.1097/01.MIB.0000441201.10454.06

    Article  PubMed  Google Scholar 

  61. Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, Muruve DA, McKay DM, Beck PL, Mawe GM, Thompson RJ, Sharkey KA (2012) Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med 18(4):600–604. https://doi.org/10.1038/nm.2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liu J, Prell T, Stubendorff B, Keiner S, Ringer T, Gunkel A, Tadic V, Goldhammer N, Malci A, Witte OW, Grosskreutz J (2016) Down-regulation of purinergic P2X7 receptor expression and intracellular calcium dysregulation in peripheral blood mononuclear cells of patients with amyotrophic lateral sclerosis. Neurosci Lett 630:77–83. https://doi.org/10.1016/j.neulet.2016.07.039

    Article  CAS  PubMed  Google Scholar 

  63. Hiken JF, Steinberg TH (2004) ATP downregulates P2X7 and inhibits osteoclast formation in RAW cells. Am J Physiol Cell Physiol 287(2):C403–C412. https://doi.org/10.1152/ajpcell.00361.2003

    Article  CAS  PubMed  Google Scholar 

  64. Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 3:1034. https://doi.org/10.1038/ncomms2023

    Article  CAS  PubMed  Google Scholar 

  65. Giaroni C, Knight GE, Ruan HZ, Glass R, Bardini M, Lecchini S, Frigo G, Burnstock G (2002) P2 receptors in the murine gastrointestinal tract. Neuropharmacology 43(8):1313–1323. https://doi.org/10.1016/s0028-3908(02)00294-0

    Article  CAS  PubMed  Google Scholar 

  66. Mizuno MS, Crisma AR, Borelli P, Castelucci P (2012) Expression of the P2X2 receptor in different classes of ileum myenteric neurons in the female obese ob/ob mouse. World J Gastroenterol 18(34):4693–4703. https://doi.org/10.3748/wjg.v18.i34.4693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Degagné E, Grbic DM, Dupuis AA, Lavoie EG, Langlois C, Jain N, Weisman GA, Sévigny J, Gendron FP (2009) P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells. J Immunol 183(7):4521–4529. https://doi.org/10.4049/jimmunol.0803977

    Article  CAS  PubMed  Google Scholar 

  68. Zhang Y, Ecelbarger CM, Lesniewski LA, Müller CE, Kishore BK (2020) P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity. Front Endocrinol (Lausanne) 11:341. https://doi.org/10.3389/fendo.2020.00341

    Article  PubMed  Google Scholar 

  69. Seye CI, Yu N, Jain R, Kong Q, Minor T, Newton J, Erb L, González FA, Weisman GA (2003) The P2Y2 nucleotide receptor mediates UTP-induced vascular cell adhesion molecule-1 expression in coronary artery endothelial cells. J Biol Chem 278(27):24960–24965. https://doi.org/10.1074/jbc.M301439200

    Article  CAS  PubMed  Google Scholar 

  70. Qian S, Shi Y, Peng Q, Senfeld J, Shen J (2022) P2Y2 receptor upregulation and signaling during adipogenesis and inflammation: a new mechanism in insulin resistance. FASEB J 36(S1). https://doi.org/10.1096/fasebj.2022.36.S1.R2881.

  71. Antonioli L, Pellegrini C, Fornai M, Tirotta E, Gentile D, Benvenuti L, Giron MC, Caputi V, Marsilio I, Orso G, Bernardini N, Segnani C, Ippolito C, Csóka B, Németh ZH, Haskó G, Scarpignato C, Blandizzi C, Colucci R (2017) Colonic motor dysfunctions in a mouse model of high-fat diet-induced obesity: an involvement of A2B adenosine receptors. Purinergic Signalling 13(4):497–510. https://doi.org/10.1007/s11302-017-9577-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Louis NA, Robinson AM, MacManus CF, Karhausen J, Scully M, Colgan SP (2008) Control of IFN-alphaA by CD73: implications for mucosal inflammation. J Immunol 180(6):4246–4255. https://doi.org/10.4049/jimmunol.180.6.4246

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank María C. Martínez-Saldaña and Sonia S. Cruz-Muñoz for their helpful advice on histological technical issues examined in this paper.

Funding

This study was funded by CONAHCYT under grant number CF-2019/21854. J.R.C.M. was supported by CONAHCYT Scholarship number 806361. E.E.V.M. was supported by “Investigadores por México”, CONAHCYT.

Author information

Authors and Affiliations

  1. Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México

    José R. Cruz-Muñoz, Eduardo E. Valdez-Morales, Tonatiuh Barrios-García & Raquel Guerrero-Alba

  2. Escuela Superior de Huejutla, Universidad Autónoma del Estado de Hidalgo, Huejutla de Reyes, Hidalgo, México

    Alma Barajas-Espinosa

  3. Centro Universitario de Investigaciones Biomédicas. Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT), Universidad de Colima, Colima, México

    Andrómeda Liñán-Rico

Authors
  1. José R. Cruz-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo E. Valdez-Morales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alma Barajas-Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tonatiuh Barrios-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrómeda Liñán-Rico
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raquel Guerrero-Alba
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: A.B.E., A.L.R., and R.G.A.; methodology: J.R.C.M., E.E.V.M, and T.B.G.; formal analysis: J.R.C.M., A.L.R., R.G.A., and E.E.V.M.; investigation: J.R.C.M., A.L.R., and R.G.A.; resources: A.L.R. and R.G.A.; data curation: J.R.C.M. and R.G.A.; writing—original draft preparation: RGA; writing—review and editing: A.B.E. and A.L.R.; supervision: A.L.R., R.G.A., T.B.G., and E.E.V.M.; project administration: A.L.R. and R.G.A.; funding acquisition: A.B.E., A.L.R., and R.G.A. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Andrómeda Liñán-Rico or Raquel Guerrero-Alba.

Ethics declarations

Ethics approval and consent to participate

This study was conducted under the guidelines from the Mexican norm (NOM-062-ZOO-1999) and approved by the ethics committee concerning animals in teaching and research at the Autonomous University of Aguascalientes (CEADI-UAA INV 010/2023).

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cruz-Muñoz, J.R., Valdez-Morales, E.E., Barajas-Espinosa, A. et al. Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes. Purinergic Signalling (2024). https://doi.org/10.1007/s11302-024-10006-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11302-024-10006-1

Keywords

Search

Navigation