Abdoulaye, Diane (2006) Stress, axe corticotrope et caracteristiques nutritionnelles et metaboliques. PhD thesis Nutrition humaine, Nutrition humaine, INAPG 2006INAP0033 p.121.

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Abstract

Interactions between stress and food intake are well recognized as being complex and

multiple. The usually actnowledged link between stress and body weight gain involves

feeding behavior alterations consisting in either a reduction or an increase of food intake

according to subjects. The first part of this work studied the influence of a stress on body

weight gain and on macronutrient selection. Studies were carried out on Wistar rats submitted

to two different food situations (experiment 1 : rats received food ad-lib ; experiment 2 : rats

were submitted to food restriction (2 feeding periods per day). The results of these two

experimental protocols showed that an acute stress (15-min of swimming/day for 3

consecutive days), applied at the onset of the dark phase, just before the usual feeding time,

induced a significant reduction in daily body weight gain in male and female Wistar rats.

Moreover stress induced increased plasma corticosterone levels and decreased of insulinemia.

Sexual dimorphism was observed regarding the macronutrient selection in response to stress.

Thus we concluded that, stress induced not only a quantitative but also a qualitative effect on

food intake. In the 2nd part of this work we focused on the genetic variability of HPA axis in

relation to the regulation of energy metabolism between two inbred strains of rats : Fischer

F344, prone to obesity and Lou, obesity resistant. The neuroendocrinological, nutritional and

metabolic comparisons showed that F344 strain presents (i) disturbances of its HPA axis

resulting in a higher secretion of corticosterone and (ii) a strong vulnerability to develop

obesity by increasing adiposity and reducing the basal metabolism compared with the Lou

strain. In the last part of this work, we used a « nutraceutic approach » : testing the influence

of a functional food (yeast extract) on stress. From our stress model developped at the point in

the first part of this thesis, this work showed the protective properties of yeast extract on stress

induced behavioral and eating disorders. These results open a new prospect on relationships

between stress and feeding behavior but also provide new elements for understanding obesity

resistance in Lou rat implying the HPA axis.

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Table of content

REMERCIEMENTS 1

RESUME 2

ABSTRACT 3

LISTES DES PUBLICATIONS ET COMMUNICATIONS 4

Posters 4

Articles scientifiques : 4

LISTE DES FIGURES ET TABLEAUX 5

SOMMAIRE 7

INTRODUCTION GENERALE 13

1 Stress : 13

1.1 Ambiguïté du concept de stress, préambule à une définition: 13

1.2 Concept de stress 14

1.3 Approche biologique du stress : historique et approche actuelle. 14

1.4 Bases physiologiques et neurophysiologiques de la réponse au stress 16

1.4.1 Phase d’alarme 16

1.4.2 Phase de résistance 17

1.4.3 Phase d’épuisement. 17

1.5 L’axe corticotrope 18

1.5.1 Description de l’axe corticotrope: 18

1.5.1.1 Le système limbique: 18

1.5.1.2 L’hypothalamus : 18

1.5.1.3 L’hypophyse : 19

1.5.1.4 glandes surrénales 19

8

1.5.2 Organisation fonctionnelle de l’axe corticotrope. 19

1.5.3 Les récepteurs aux corticostéroïdes 21

1.5.4 Rythme circadien 22

1.5.5 Activation de l’axe corticotrope : 22

1.5.6 Le rétrocontrôle négatif 23

1.5.7 Rôles des corticostéroïdes 24

1.5.7.1 Rôle sur le système immunitaire 24

1.5.7.2. Rôle sur le métabolisme de l’eau et des électrolytes 25

1.5.7.3 Rôle sur le comportement 26

1.5.7.4 rôles sur la nutrition : 26

2 Relation stress et comportement alimentaire. 28

2.1 Généralités sur le métabolisme énergétique et comportement alimentaire 28

2.1.1 Métablisme énergétique : 28

2.1.2 Le comportement alimentaire 30

2.1.2.1 Description du comportement alimentaire 30

2.1.2.2 Rythmicité de la prise alimentaire (PA) 30

2.1.2.3 Description d’un épisode de prise alimentaire 31

2.1.2.4 Le comportement alimentaire : un comportement adaptatif 31

2.1.2.5 Régulation quantitative du métabolisme énergétique 32

2.1.2.6 Régulation qualitative du métabolisme énergétique 34

2.1.2.7 Bases physiologiques et neurophysiologiques du comportement alimentaire 37

2.2 Stress et comportement alimentaire 43

2.2.1 Le stress et ses effets sur la prise alimentaire 43

2.2.1.1 Chez l’homme : 43

2.2.1.2 Chez le rat : 44

9

2.2.2 Stress et choix alimentaire 44

2.2.3 Mécanismes centraux impliqués dans le contrôle de la prise alimentaire par le stress 46

3 Stress et obésité 48

3.1 Variabilité génétique de l’axe corticotrope 48

3.1.1 Chez l’homme : 48

3.1.2 Chez l’animal 49

3.2 Axe corticotrope et physiopathologie de l’obésité 50

3.2.1 L’obésité 50

3.2.2 Epidémiologie 50

3.2.3 Les causes de l'obésité 52

3.3 Fonctionnement de l’axe corticotrope et obésité : 52

3.3.1 Chez l’homme : 53

3.3.2 Chez l’animal 53

TRAVAUX PERSONNELS 56

ETUDE 1 : RELATION STRESS ET COMPORTEMENT ALIMENTAIRE :

INFLUENCE DU STRESS SUR LE CHOIX ALIMENTAIRE. 58

Résumé de l’article : 59

Conclusion de l’étude 60

ETUDE 2 : VARIABILITE GENETIQUE DE L’AXE CORTICOTROPE ET

REGULATION DU METABOLISME ENERGETIQUE. 88

But et objectifs 90

Les particularités nutritionnelles et métaboliques du rat Lou : 90

A. ETUDE FONCTIONNELLES DES SYSTEME NEUROENDOCRINIENS 92

1 Matériel et Méthodes : 92

1.1. Animaux : 92

1.2. Activité et réactivité de l’axe corticotrope : 92

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1.2.1 Corticostéronémie basale sur 24h : 92

1.2.2 Corticostéronémie après le stress : 92

1.3. Efficacité des récepteurs aux corticostéroïdes (GR et MR) 92

1.3.1 Efficacité GR 93

1.3.1.1 Rétrocontrôle négatif : 93

1.3.2 Efficacité MR 93

2 Analyses statistiques 94

3 Résultats 95

3.1 Activité/réactivité de l’axe corticotrope 95

3.1.1 Cycle nycthéméral de la corticostéronémie 95

3.1.2 Réponse au stress de contention 96

3.2 Efficacité aux récepteurs corticoïdes 96

3.2.1 Efficacité GR : 96

3.2.1.1 Glycémie 96

3.2.1.2 Numération-formule 97

3.2.2 Efficacité MR 98

3.2.2.1 Rapport Na/K urinaire 98

4 Discussion : 99

B. ETUDE COMPARATIVE DES CARACTERISTIQUES NUTRITIONNELLES

ET METABOLIQUES 101

Résumé de l’étude2: 101

Résumé de l’étude 3 : 102

Conclusion de l’étude 103

ETUDE 3 : PROCESSUS DE REGULATION ET D’ADAPTATION AU STRESS :

MISE EN APPLICATION A L’ETUDE DE L’EFFET D’UN ALIMENT FONCTIONNEL

SUR LE STRESS 120

Introduction 121

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1 Matériel et méthodes 122

1.1 Animaux, alimentation et complémentation 122

1.2 Procédure expérimentale 123

1.2.1 Procédure d’application des conditions de stress 123

1.2.2 Protocole suivi 123

1.2.3 Test du niveau d’anxiété des animaux 123

1.2.4 Dispositif du test de stress en openfield 124

2 Analyses statistiques : 124

3 Résultats 125

3.1 Evolution relative du poids des animaux (%) 125

3.2 La prise alimentaire 125

3.3 Paramètres d’anxiété 127

3.4 Paramètres biologiques : 128

4 Conclusion de l’étude: 128

DISCUSSION GENERALE 130

CONCLUSION ET PERSPECTIVES 134

REFERENCES BIBLIOGRAPHIQUES 145

ANNEXES 165

Annexe 1 : Procédure chirurgicale de cathérisation de la veine cave via la veine jugulaire165

Protocole opératoire 165

Annexe 2 : Thermogenèse par mesure de l’activité des mitochondries du TAB 167

Annexe 3 : Dosage d’Insuline par RIA 168

Annexe 4 : Dosage de Leptine en RIA 170

Annexe 5 : Dosage de corticostérone par RIA 172

Annexe 6: Tableaux de composition des différents régimes 174

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Annexe 7 : implantation de cathéter dans la veine jugulaire droite chez le rat 175

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