Paulino, Gabriel (2007) Mechanisms and Pathways in Adaptation of the Detection of Dietary Fat. PhD thesis Physiology of Nutrition, AgroParistech 2007AGPT0064 p.174.

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Abstract

The global population is getting obese. From developed to developing countries the pandemic is now irrefutable. Research focusing on obesity has increased exponentially over the past few decades but yet no solution has been found. Dietary fat has been blamed for this epidemic because people adapted to a high-fat diet develop hyperphagic behavior and therefore become obese. The aim of this work was to understand the mechanisms by which a high-fat diet can induce hyperphagia starting from behavorial studies to the molecular biology behind it. These studies have been conducted in two animal models: Rattus norvegicus and Mus musculus. The results of these studies have shown that rats subjected to a chronic high-fat diet become hyperphagic upon vagal insensitivity to dietary fat compared to rats fed a low-fat diet. Also, we demonstrated that the cholecystokinin receptor 1 plays an important role in the detection of dietary fat. Finally, we proposed a molecular model of the adaptation of the nodose ganglia by which a decreased expression of the leptin receptor (anorexigenic) was associated with an increased expression of the cannabinoid receptor (orexigenic). This suggests one of the many mechanisms underlying hyperphagic behavior in rats fed a chronic high-fat diet. In conclusion, we have shown that diet is able to interact with genes involved in short-term regulation of food intake. These findings are critical in understanding the potential causes of obesity. The human genome has evolved from the direct interaction between environment and diet; it is not counterintuitive to think that diet can influence gene expression. Why does a high-fat diet induce a hyperphagic response in the organism? Can we find answers by looking back in time and observe how people, diet and environment evolved together? Does the thrifty gene theory make sense in this context? These are questions that need to be answered in order to find a solution to obesity.

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Table of content

Acknowledgements 2



table of contents 4



background 5



introduction 9



chapter 1 28

adaptation to dietary fat 28



chapter 2 49

adaptation of lipid-induced satiation is not dependent on caloric density in rats 49



chapter 3 84

cck1 receptor is essential for normal meal patterning in mice fed high fat diet 84



chapter 4 107

adaptation to a high fat diet alters the normal receptors expression involved in the detection of dietary fat 107



chapter 5 137

future experiments 137



conclusion 142



references 144

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