title: A role for intestinal TLR4-driven inflammatory response during activity-based anorexia.
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.
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Rouen University Hospital, Nutrition Department, Rouen, France.
authors: Liliana
authors: L
authors: Belmonte
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Rouen University Hospital, Nutrition Department, Rouen, France.
authors: Najate
authors: N
authors: Achamrah
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors: Séverine
authors: S
authors: Nobis
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors: Charlène
authors: C
authors: Guérin
authors: Normandie Univ, UR, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Flow cytometry facility CyFlow, Rouen, France.
authors: Gaëtan
authors: G
authors: Riou
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors: Christine
authors: C
authors: Bôle-Feysot
authors: Normandie Univ, UR, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Flow cytometry facility CyFlow, Rouen, France.|INSERM, U905, Rouen, France.
authors: Olivier
authors: O
authors: Boyer
authors: Normandie Univ, UR, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|INSERM, U1096, Rouen, France.
authors: Vincent
authors: V
authors: Richard
authors: Normandie Univ, UR, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Animal Behavior Platform SCAC, Rouen, France.
authors: Jean Claude Do
authors: JC
authors: Rego
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Rouen University Hospital, Nutrition Department, Rouen, France.
authors: Pierre
authors: P
authors: Déchelotte
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors: Alexis
authors: A
authors: Goichon
authors: Normandie Univ, UR, Rouen, France.|INSERM unit 1073, Rouen, France.|Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Rouen University Hospital, Nutrition Department, Rouen, France.
authors: Moïse
authors: M
authors: Coëffier
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000378:metabolism*; D007031:Hypothalamus / Q000276:immunology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015431:Weight Loss / Q000235:genetics
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4