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Table of contents
GENERAL INTRODUCTION
I. Fast development of aquaculture industry
II. Fish nutrition, aquafeeds and the bottleneck in aquaculture
III. Dietary carbohydrates: promising substitutes for FM and FO as well as challenging risks for arnivorous fish
IV. Epigenetics, a potential mechanism in phenotypic adaptation
V. General objectives of the present thesis project
CHAPTER 1 INTRODUCTION AND LITERATURE REVIEW
1.1 Overview of epigenetics
1.1.1 DNA methylation
1.1.2 Histone modifications
1.1.3 Nucleosome remodelling
1.1.4 Non-coding RNA
1.2 DNA methylation
1.2.1 DNA methylation machinery and pathways
1.2.2 DNA methylation dynamics during gametogenesis and embryogenesis
1.2.3 DNA methylation regulation by nutrients, oxidative stress and hypoxia
1.2.4 Global DNA hyper and hypomethylation and the related consequences
1.2.5 Non-CpG methylation and its functional highlights
1.2.6 Potential roles of 5-hmC, 5-fC and 5-caC
1.3 Epigenetics and metabolic programming
1.3.1 Concept of metabolic programming
1.3.2 Programmed phenotypes and suspected epigenetic mechanisms: selected examples from invertebrates up to mammals
1.3.3 Metabolic programming for fish nutrition in aquaculture
1.4 Rainbow trout as a model to study epigenetics and programming:-understanding the low dietary carbohydrates utilisation and glucose-intolerant phenotype
1.4.1 Embryonic development of rainbow trout
1.4.2 Dietary carbohydrate utilisation and glucose metabolic pathways in trout
1.4.3 Hypotheses to explain the poor dietary carbohydrate use in rainbow trout
CHAPTER 2 HYPOTHESES AND OBJECTIVES
2.1 Question I: How many DNA methylation-related genes are preserved in trout genome, and what are their evolutionary origins?
2.2 Question II: What are the nutritional factor(s) triggering the hepatic global DNA hypomethylation in trout after feeding a high carbohydrates/low protein diet? And what are the detail mechanisms involved in this demethylation process?
2.3 Question III: Can DNA hypomethylation phenotype and glucose metabolism be modified through metabolic programming strategy?
CHAPTER 3 RESULTS
3.1 Flowchart of thesis design
3.2 Part 1 Evolutionary history of DNA methylation related genes in chordates: new insights from multiple whole genome duplications -Publication1
3.3 Part 2: Factors triggering hepatic global DNA hypomethylation phenotype in trout fed a high carbohydrate-low protein diet and the detail mechanisms – Publication 2
3.4 Part 3: Metabolic programming effects of hypoxia during early development and/or high carbohydrate dietary stimulus at first feeding on epigenetic landscapes and glucose metabolism in trout juveniles
3.4.1 Acute hypoxia & high-carbohydrates diets as stimuli
3.4.1.1 Short-term effects: Exposure to an acute hypoxic stimulus during early life affects the expression of glucose metabolism-related genes at first-feeding in trout – Publication 3
3.4.1.2 Long-term effects: Long-term programming effect of embryonic hypoxia exposure and high-carbohydrate diet at first feeding on glucose metabolism in juvenile rainbow trout – Publication
3.4.2 Chronic hypoxia & high-carbohydrate diets as stimuli: Programming of the glucose metabolism in rainbow trout juveniles after chronic hypoxia at hatching stage combined with a high dietary carbohydrate: Protein ratios intake at first-feeding – Publication 5
CHAPTER 4 DISCUSSION AND PERSPECTIVES
4.1 Part I Further investigation about the roles of DNA methylation /demethylation related genes in trout
4.1.1 Conservation of the DNA methylation-related enzymes in trout (even for the paralogs) but neo-/sub-functionalisation
4.1.2 Evolution of the expression territories of dnmt, tet and tdg genes
4.2 Part II Hepatic global DNA hypomethylation after feeding a high carbohydrate/low protein diet in trout: causes and beyond
4.2.1 New insights on dietary factors that induced global non-CpG hypomethylation in the liver of trout
4.2.2 Limitations and obstacles in the experimental design of the present study
4.3 Part III Programming of glucose metabolism in trout: achievement and challenges
4.3.1 How to ‘program’ fish: selection of the type of stimulus and the ‘’windows of metabolic plasticity’
4.3.2 Metabolic programming of trout with hypoxia: early hypoxic history induced alteration in glucose metabolism in juvenile trout- highlights of the effects on glucose transporter related genes (the gluts)
4.3.3 Mechanisms of programming: potential epigenetic mechanisms linked to the long-term programming effects
CHAPTER 5 GENERAL CONCLUSIONS: NEW MAJOR KNOWLEDGE LEARNED FROM THE PRESENT THESIS
5.1 What new knowledge did we obtain to explain the poor carbohydrate utilisation in trout?
5.2 Is it possible to improve the dietary carbohydrate utilisation of trout with metabolic programming strategy?
5.3 What are the potential impacts of the presnet thesis on aquaculture?
BIBLYOGRAPHY
ANNEXES
