The neuroanatomical  expression profile of novel  membrane proteins. : The effect of macronutrients on gene expression.

Abstract: Worldwide obesity is an increasing problem. Apart from the fact that obesity greatly  impairs the health, quality and length of life for the affected individuals, it is also has the  potential to become a major socioeconomic problem in a near future. However preventive  actions require an understanding of the cause. Before the psychological influence on  eating can be evaluated a profound understanding of the biological regulatory system and  how this interacts with the food consumed is required. On the assumption that food  consumption is regulated by interplay between food and genes, the food itself may  influence the genes that regulate consumption, hence change the expression levels of the  genes regulating food intake.     To evaluate the interplay between food and gene expression, the project contained several  parts, reflecting different aspects of the area of research. The feeding studies had in  common that they were initial trials in a larger project. The results of these will be  evaluated and used in combination with further studies.     The mice typed for food preference illustrate the complexity of the feeding regulatory  system by pointing out the differences between individuals even in a relatively small  group of animals. Mice in general like food high in fat and here the animals that showed a  preference for sugar also showed a significant increase in their intake of chow. Since  chow consists mainly of carbohydrates the results might indicate a preference not for  sucrose in particular but for carbohydrates in general. The effect this may have on other  studies is still unclear as further studies are needed to determine whether the difference  may be the result of an innate genetic difference.      Leucine has been previously shown to reduce the total caloric intake. When given in  combination with palatable food the addition of Leucine primarily reduced the intake of  chow. From a dietary perspective this would translate to a preference to sweets and fast  food at the expense of food with more nutritious content.     The RT-PCR analysis’s gives clues to how the energy regulatory circuitry responds to the  intake of selected macronutrients. When it comes to gene expression there is a significant  effect of macronutrients on the gene expression levels. The common theme for many of  the genes tested seems to be down regulation of satiety signals, as if to support over  feeding on palatable diets and in many cases sucrose in particular.     The intake of macronutrients such as sugar or fat has been showed to have an effect on  the feeding regulatory circuitry, demonstrated by the change in gene expression levels.   The response to said macronutrients is site specific which is clearly shown both by RTPCR analysis of samples from different parts of the brain, such as the brainstem or  hypothalamus, and by immunohistochemistry of selected areas. The  immunohistochemistry also confirms that the novel Oxytocin receptor-antagonist, who is  injected IP, actually passes over the blood-brain barrier and has an actual affect on the  regions of interest. The areas affected by the antagonist can be visualized and identified  through the staining of active sites.