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Table of contents
RÉSUMÉ FRANÇAIS
A. Contexte du projet
1. Les altérations du tissu adipeux dans les maladies métaboliques
2. Les altérations de l’intestin et du microbiote intestinal dans les malacies métaboliques
B. Objectifs et principaux résultats
1. Etude I: L’adaptation du tissu adipeux à un stress métabolique induit par l’isomère trans10, cis12 de l’acide linoléique engage des macrophages anti-inflammatoires.
Introduction
Résultats
Résultats complémentaires
Conclusion
2. Etude II: Effet de deux souches de probiotiques sur la prise de poids et le statut glycémique chez la souris rendue obèse par un régime hyperlipidique
3. Conclusion générale
C. Contribution à des publications présentées en annexe
1. Publication 2
2. Publication 3
3. Publication 4
LIST OF FIGURES
LIST OF TABLES
ABBREVIATIONS
INTRODUCTION
A. Metabolic diseases
1. Metabolic syndrome
2. Overweight and obesity
3. Diabetes mellitus type II
4. Lypodistrophic syndromes
B. Metabolic diseases: the available models
1. Mouse models of obesity
Leptin-deficient mice
Leptin receptor-deficient mice
High fat diet-induced obesity
2. Lipodystrophic mouse models
PPARγ-deficient mice
Transgenic aP2-SREBP-1c mice
A-ZIP/F-1 mice
C. The metabolic organs
1. Adipose tissue: functions and dysfunctions
Metabolic and endocrine functions
Adipose tissue plasticity
Adipose tissue immunity and inflammation
2. Liver: functions and dysfunctions
Metabolic functions
Non-alcoholic fatty liver disease
3. Intestine: functions and dysfunctions
4. Muscle: functions and dysfunctions
D. Metabolic diseases: Innate and adaptive immunity
1. Innate immunity
Mast cells
Neutrophils
Macrophages
Dendritic cells
Natural killer cells
2. Adaptive immunity
Lymphocytes
Natural killer T- cells
Helper T- cells
Gamma delta T- cells
B lymphocytes
3. Immunological memory
4. Immunity and inflammation: chemokines and other recruitment factors
Adipochemokines
Cathepsins
Galectins
E. Adipose tissue: cellular and structural alterations in obesity
1. Adipocytes: functions and dysfunctions
2. Extra cellular matrix: composition and pathophysiology
3. Extra cellular matrix: a dynamic structure
4. Adipose tissue fibrosis in obesity and after drastic weight loss
F. A cross-road between metabolism and immunity
1. Nutrient-sensing and metabolism
2. Toll like receptors (TLRs)
3. G-protein coupled receptors (GCPRs)
G. Conjugated fatty acids: the t10,c12-CLA model
1. Conjugated fatty acids
Conjugated linoleic acid (CLA)
CLA isomers: experimental effects
2. A murine model of lypoatrophic syndrome: t10, c12 CLA
Adipose tissue and t10, c12 CLA
Liver and t10, c12 CLA
Intestine and t10, c12 CLA
Pancreas and t10, c12 CLA
Muscle and t10, c12 CLA
Immunity and t10,c12-CLA
H. Intestinal microflora and metabolic diseases
1. Microbiota composition: functions and dysfunctions
2. Symbiosis between the host and the microbiota
3. Microflora modulation: potential therapeutics
4. Effectiveness of probiotic and prebiotic interventions
RESEARCH PROJET: PURPOSE AND RESULTS
A. Hypothesis and models used
B. Study I: Adipose tissue plasticity in response to short-term trans 10, cis12 conjugated linoleic acid (CLA) adimistration in mice
C. PUBLICATION 1
D. Complementary results of study I
1. WAT nutrient-sensing in response to CLA
2. WAT plasticity in response to CLA
3. Effects of CLA adminsitration on transcription factors of the IRF family
4. Effects of CLA administration on the intestine: barrier function
5. Effects of CLA administration on the intestine: microbiota
6. Reversibility: permeability and intestinal ecology
7. Effects of CLA administration on the liver
8. Are the CLA effects on WAT indirectly mediated by macrophages?
E. Conclusions
STUDY II: PROBIOTIC ADMINISTRATION IN DIET-INDUCED OBESE MICE: EFFECT OF BODY WEIGHT GAIN AND GLYCEMIC STATUS.
A. Purpose
B. The experimental model
1. Methods
2. Effects of probiotics on body weight and adiposity
3. Effects of probiotics on glycemic status
4. Effects of probiotics on plasma variables
C. Conclusions
A. Contribution of adipose tissue to metabolic deregulation
B. Adipose tissue plasticity and metabolic consequences
C. The future of probiotics to improve metabolic status?
D. Conclusions
BIBLIOGRAPHY
