Tesis doctoral de Almudena Lomba Piquer
Obesity can be defined as an excessive accumulation of body fat, which is attributed to a state of chronic positive energy balance induced by several factors, such as inadequate dietary habits, sedentary physical activity patterns and genetic interactions. Experimental studies have demonstrated that not only the amount of energy, but also the dietary macronutrient composition may be involved in obesity development. In this sense, nutritional, chemical and physical factors have the potential to alter gene expression and modify adult disease susceptibility in various ways through changes in the epigenome such as dna methylation. Recent studies indicate that environmental factors and diet can perturb the way genes are controlled by dna methylation and covalent histone modifications. in order to assess whether the macronutrient composition of the diet could be related to the gene expression and epigenetic regulation in obesity development, male wistar rats were randomly assigned to four different dietary groups with different macronutrient proportions: control (c; n=12), high sucrose diet (hs; n=13), high fat-sucrose diet (hfs; n=12) and high fat diet (hfd; n=11). These diets were supplied during eight weeks as a pair-fed model. After sacrifice, gene expression related to lipid, glucose and oxidative metabolism, as well as epigenetic changes in these genes were studied in liver and epididymal fat. our hfd, hfs and hs groups showed higher body weight gain and adiposity compared to c. Regarding biochemical values, we observed a significant reduction in cholesterol and hdl cholesterol in the hs and hfs groups compared to c. Dietary treatment caused a significant reduction in serum triglycerides and a significant increase in levels of hepatic malondialdehyde in hfs group and liver triglycerides in the hfs and hfd groups. Hepatic gene expression studies showed an increase in hadhb (β-oxidation) in the hfs group than in c group. Gene expression in epididymal adipose tissue showed a significant reduction in ndufb6 in the groups hs and hfd compared to c group. Regarding epigenetic studies, changes in fas and ndufb6 promoter methylation were observed in epididymal adipose tissue in hfd group compared to c group. these results suggest that the intake of excess fat diets, fat and simple sugars or high proportion of simple sugars and low of complex sugars induces excess weight gain independently of total energy intake. These diets can also produce epigenetic modifications (dna methylation) in the methylation pattern of key metabolic genes in adipose tissue that may influence their gene expression and explain some of the metabolic alterations.
Datos académicos de la tesis doctoral «Estudio de la expresión y el patrón de metilación de genes del metabolismo energético en modelos dietéticos de obesidad con diferente distribución de macronutrientes«
- Título de la tesis: Estudio de la expresión y el patrón de metilación de genes del metabolismo energético en modelos dietéticos de obesidad con diferente distribución de macronutrientes
- Autor: Almudena Lomba Piquer
- Universidad: Navarra
- Fecha de lectura de la tesis: 16/09/2010
Dirección y tribunal
- Director de la tesis
- Fermin I. Milagro Yoldi
- Tribunal
- Presidente del tribunal: florencio Marzo pérez
- edurne Simon magro (vocal)
- Juan José Hernández morante (vocal)
- María Izquierdo pulido (vocal)