A Role for Intestinal TLR4-driven Inflammatory Response During Activity-based Anorexia

Overview

Journal Sci Rep

Specialty Science

Date 2016 Oct 26

PMID 27779218

Citations 20

Authors

Liliana Belmonte

Najate Achamrah

Severine Nobis

Charlene Guerin

Gaetan Riou

Christine Bole-Feysot

Olivier Boyer

Vincent Richard

Jean Claude do Rego

Pierre Dechelotte

Alexis Goichon

Moise Coeffier

Affiliations

Soon will be listed here.

Abstract

Anorexia nervosa (AN) is associated with low-grade systemic inflammation and altered gut microbiota. However, the molecular origin of the inflammation remains unknown. Toll-like receptors are key regulators of innate immune response and their activation seems also to be involved in the control of food intake. We used activity-based anorexia (ABA) model to investigate the role of TLR4 and its contribution in anorexia-associated low-grade inflammation. Here, we found that ABA affected early the intestinal inflammatory status and the hypothalamic response. Indeed, TLR4 was upregulated both on colonic epithelial cells and intestinal macrophages, leading to elevated downstream mucosal cytokine production. These mucosal changes occurred earlier than hypothalamic changes driving to increased levels of IL-1β and IL-1R1 as well as increased levels of plasma corticosterone. Paradoxically, TLR4-deficient mice exhibited greater vulnerability to ABA with increased mortality rate, suggesting a major contribution of TLR4-mediated responses during ABA-induced weight loss.

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References

Jesus P, Ouelaa W, Francois M, Riachy L, Guerin C, Aziz M . Alteration of intestinal barrier function during activity-based anorexia in mice. Clin Nutr. 2013; 33(6):1046-53. DOI: 10.1016/j.clnu.2013.11.006. View

Klenotich S, Dulawa S . The activity-based anorexia mouse model. Methods Mol Biol. 2012; 829:377-93. DOI: 10.1007/978-1-61779-458-2_25. View

Wong S, Pinkney J . Role of cytokines in regulating feeding behaviour. Curr Drug Targets. 2004; 5(3):251-63. DOI: 10.2174/1389450043490532. View

Plata-Salaman C, Ilyin S, Gayle D, Flynn M . Gram-negative and gram-positive bacterial products induce differential cytokine profiles in the brain: analysis using an integrative molecular-behavioral in vivo model. Int J Mol Med. 1998; 1(2):387-97. DOI: 10.3892/ijmm.1.2.387. View

Fasano A . Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012; 10(10):1096-100. PMC: 3458511. DOI: 10.1016/j.cgh.2012.08.012. View

Laviano A, Meguid M, Rossi-Fanelli F . Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol. 2003; 4(11):686-94. DOI: 10.1016/s1470-2045(03)01247-6. View

Achamrah N, Nobis S, Breton J, Jesus P, Belmonte L, Maurer B . Maintaining physical activity during refeeding improves body composition, intestinal hyperpermeability and behavior in anorectic mice. Sci Rep. 2016; 6:21887. PMC: 4764812. DOI: 10.1038/srep21887. View

Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A . Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000; 355(9214):1518-9. DOI: 10.1016/S0140-6736(00)02169-3. View

Luo H, Guo P, Zhou Q . Role of TLR4/NF-κB in damage to intestinal mucosa barrier function and bacterial translocation in rats exposed to hypoxia. PLoS One. 2012; 7(10):e46291. PMC: 3474812. DOI: 10.1371/journal.pone.0046291. View

10.

Suenaert P, Bulteel V, Den Hond E, Hiele M, Peeters M, Monsuur F . The effects of smoking and indomethacin on small intestinal permeability. Aliment Pharmacol Ther. 2000; 14(6):819-22. DOI: 10.1046/j.1365-2036.2000.00754.x. View

11.

Hu G, Gong A, Roth A, Huang B, Ward H, Zhu G . Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathog. 2013; 9(4):e1003261. PMC: 3617097. DOI: 10.1371/journal.ppat.1003261. View

12.

Kim S . Animal models of eating disorders. Neuroscience. 2012; 211:2-12. PMC: 3351502. DOI: 10.1016/j.neuroscience.2012.03.024. View

13.

Tennoune N, Chan P, Breton J, Legrand R, Chabane Y, Akkermann K . Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders. Transl Psychiatry. 2014; 4:e458. PMC: 4350527. DOI: 10.1038/tp.2014.98. View

14.

Davis J, Gabler N, Walker-Daniels J, Spurlock M . Tlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat. Obesity (Silver Spring). 2008; 16(6):1248-55. DOI: 10.1038/oby.2008.210. View

15.

Shi H, Kokoeva M, Inouye K, Tzameli I, Yin H, Flier J . TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006; 116(11):3015-25. PMC: 1616196. DOI: 10.1172/JCI28898. View

16.

Pisetsky D, Trace S, Brownley K, Hamer R, Zucker N, Roux-Lombard P . The expression of cytokines and chemokines in the blood of patients with severe weight loss from anorexia nervosa: an exploratory study. Cytokine. 2014; 69(1):110-5. PMC: 4411080. DOI: 10.1016/j.cyto.2014.05.018. View

17.

Armougom F, Henry M, Vialettes B, Raccah D, Raoult D . Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One. 2009; 4(9):e7125. PMC: 2742902. DOI: 10.1371/journal.pone.0007125. View

18.

Ten Oever J, Kox M, van de Veerdonk F, Mothapo K, Slavcovici A, Jansen T . The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases. BMC Immunol. 2014; 15:55. PMC: 4240815. DOI: 10.1186/s12865-014-0055-y. View

19.

Candia E, Diaz-Jimenez D, Langjahr P, Nunez L, De la Fuente M, Farfan N . Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients. Immunobiology. 2011; 217(6):634-42. DOI: 10.1016/j.imbio.2011.10.023. View

20.

Tropp J, Markus E . Effects of mild food deprivation on the estrous cycle of rats. Physiol Behav. 2001; 73(4):553-9. DOI: 10.1016/s0031-9384(01)00487-5. View