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Lucile Capuron, Julie Lasselin et al. dans Brain Behav Immun.

L'inflammation systémique de bas-grade est impliquée dans les déficits de flexibilité cognitive chez le sujet obèse

Le 20 juin 2016

Low-grade inflammation is a major contributor of impaired attentional set shifting in obese subjects. Lasselin J, Magne E, Beau C, Aubert A, Dexpert S, Carrez J, Layé S, Forestier D, Ledaguenel P, Capuron L. Brain Behav Immun. 2016 May 17. pii: S0889-1591(16)30122-2. doi: 10.1016/j.bbi.2016.05.013. [Epub ahead of print] PMID:27223095




Historique :
 Obesity represents currently a major public health concern. Not only related to a greater risk of cancers, metabolic, cardiovascular and musculoskeletal diseases, this disorder is also associated with a higher occurrence of behavioral alterations, including impairment in cognitive functioning. In particular, deficits in cognitive flexibility ( i.e. the ability to shift between one rule to another) have been reported in some obese individuals. Although this alteration is critical, as it can interfere with obesity management and treatment, the underlying mechanisms remain unknown. One potential hypothesized mechanism is inflammation. 

Obesity is indeed characterized by a small but chronic production of inflammatory factors, which may act in the brain and contribute to cognitive alterations. In this study, we sought to assess whether systemic low-grade inflammation (determined by circulating C-reactive [CRP] protein levels) plays a role in altered cognitive flexibility in obese individuals. We showed that obese individuals with higher levels of CRP exhibit reduced cognitive flexibility, while obese individuals with lower levels of this inflammatory marker performed similarly than the normal-weight control group. In addition, our results indicate that combination of obesity and higher level of inflammation predicts significant impairment in cognitive flexibility, while obesity or inflammation alone do not. 

Altogether, these findings support the notion that inflammation represents a major contributor of altered cognitive flexibility in obesity and that a subpopulation of obese subjects (i.e., those with higher level of inflammation) is at higher risk for this impairment. 

Résumé : Impairment in cognitive flexibility and set shifting abilities has been described in obesity. This alteration is critical as it can interfere with obesity management strategies. Recent evidences suggest that chronic low-grade inflammation may be involved in cognitive deficits associated with obesity, but the potential involvement in reduced flexibility remains unknown. 

The objective of this study was to assess the contribution of low-grade inflammation, determined by circulating levels of high-sensitivity C-reactive protein (hsCRP), in reduced cognitive flexibility and shifting abilities of obese subjects relatively to a group of non-obese participants. Performance in the intra/extra-dimensional set shift (IED) test, extracted from the CANTAB, was assessed in 66 obese subjects and 20 non-obese participants. 
Obese subjects with concentrations of hsCRP above 5mg/L exhibited reduced performance on the IED test in comparison to obese subjects with lower levels of hsCRP and non-obese participants. This difference was particularly manifest in the number of errors made during the extra-dimensional shift (EDS errors). 
In contrast, performance before the extra-dimensional shift was spared. Linear regression analyses revealed that the association between obesity and IED alterations was significant only when the condition hsCRP >5mg/L was entered in the model. 
These findings are important as they indicate that, rather than obesity itself, low-grade inflammation represents a major contributor of IED performance in obese subjects.


Lucile Capuron, PhD, Research Director, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro) INRA UMR 1286 - Bordeaux University (lucile.capuron @ bordeaux.inra.fr)
Dernière mise à jour le 20.06.2016

Auteurs


Julie Lasselin,
PhD, Post-doc Institute of Medical Psychology and Behavioral Immunobiology, Universitätsklinikum Essen, 45 122 Essen, Germany

 

Lucile Capuron, PhD, DR INRA Laboratoire de Nutrition et Neurobiologie Intégrée (NutriNeuro), UMR 1286 INRA-Université de Bordeaux


Financement FRM de 250.000 euros  pour Lucile Capuron le 20 Juin 2016
« Rôle de l'indoléamine 2,3-dioxygénase (IDO) dans la physiopathologie et le traitement de la dépression majeure » dans le cadre  de l’appel à projet « Physiopathologie des maladies psychiatriques », visant à analyser les mécanismes physiopathologiques de la dépression.