FATTY ACIDS

Author: SERRANO CRIADO ANTONIA M..
Year: 2004.
University: MÁLAGA [www.uma.es].
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS (UNIVERSIDAD DE MÁLAGA).

Summary: INTRODUCTION: oleiletanolamida (OAS) is an endogenous mediator belonging to the family of aciletanolamidas. Unlike other aciletanolamidas as anandamide, OAS shows no affinity for the cannabinoid receptor identified thus far but has recently been described that the OAS is an endogenous ligand receptor peroxisome proliferators activated by a subtype (PPAR-a), a transcription factor that regulates the expression of genes involved in lipid metabolism. Moreover, the record of those who have described the OAS as a satiety factor that inhibits peripheral intake and body weight gain. OBJECTIVES: Based on these data, the main objective of this work was to study the role of the OAS in the liver and its effects on the regulation of metabolism under physiological conditions, seeking their potential therapeutic application in pathological processes as is the induced hepatic steatosis piloted by the administration of alcohol or tween 20 (detergent ionic not used as a vehicle of the OAS in this study). METHODS: In this study have been used rats wistar male and male mice not mutated or with a mutation to inactivate the recipient PPAR- a. The animals were acute or chronic treatment with OAS tween 20 or ethanol and were extracted blood and liver to carry out a series of biochemical analysis (analysis of fatty acids) and molecular (quantification of the level of mRNA and protein enzymes involved in lipid metabolism). RESULTS AND DISCUSSION: The OAS acts as a lipid-lowering agent that affects the metabolism of lipids in the liver, where it is located mainly receiver PPAR- a. This effect of the OAS is characterized by peripheral fat mobilization and activation of lipolysis. This study has found that the tween 20, a detergent used with great frequency as a vehicle in the dissolution of compounds lipofílicos induces lipid metabolism by promoting the development of fatty liver in the long term. The toxic effect is mediated by the induction of the enzyme SCD-I, principal point of the regulation of the synthesis of monounsaturated fatty acids. The OAS is capable of reversing the toxic effect of tween 20 to inhibit the expression of mRNA and enzyme activity SCD-I in the liver. This. Protective effect of the OAS is mediated by the recipient PPAR- a. Finally, it has also been seen that the OAS induces a dose of glucose intolerance after an overload consequence of the impact of OAS on adipose tissue by inhibiting both basal glucose uptake as induced insulin. All these results point to the development of therapeutic applications based on the effects of the OAS or its mechanisms of action.

Author: MUÑOZ FORERO SERGIO ANTONIO.
Year: 2005.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE VETERINARIA.
Place of preparation: FACULTAD DE VETERINARIA.

Summary: Obesity and diabetes type 2 have become the two major epidemics in the developed and developing (James, 2004; Zimmet et al., 2001). Knowledge of the causes and mechanisms that trigger the development of obesity, insulin resistance and diabetes type 2 is of vital importance for further prevention and treatment. Both production glicerol-3-fosfato as obtaining free fatty acids are essential for the synthesis of triglycerides in adipose tissue. Therefore, primary metabolic alterations in adipose tissue to increase obtaining glicerol-3-fosfato could increase their ability to store fat, leading to the development of obesity, insulin resistance and diabetes type 2. Under physiological conditions, it is considered that the adipocyte produces glicerol-3-fosfato from glucose during post, or through the gliceroneogénesis during fasting. Thus, in the first part of this study, we analyzed the effects of an increase in gliceroneogénesis fat through the overexpression of phosphoenolpyruvate carboxiquinasa (PEPCK) in transgenic mice. The overexpression of PEPCK led to an increase in re-esterification of fatty acids and higher deposit lipids in adipose tissue. However, while these animals showed obesity hypertrophic showed a sensitivity to insulin and glucose tolerance similar to the controls. This was probably due to the absence of high levels of FFAs, and leptin circulating TNF, together with the absence of deposit of fat in adipose tissue and no high levels of serum adiponectina. In order to explore whether an increase in the re-esterification of fatty acids was able to offset the increase in serum FFAs and the insulin resistance induced by a high fat diet, transgenic animals aP2-PEPCK were fed with this type diet for a short period. However, these animals had a severe morbid obesity and insulin resistance and glucose intolerance respect to the controls. Therefore, the combined effects of high lipid diet along with the increasing the re-esterification of fatty acids in adipose tissue, probably saturaban its ability to store fat. That led to the deposition of lipids in the liver and hypertriglyceridemia. Furthermore, the accumulation of lipids in brown adipose tissue decreased its ability termogénica. This probably contributed to obesity and insulin resistance were so severe that these transgenic animals fed a diet high in fat. These results suggest that the regulation of the ability of white adipose tissue to store fat is crucial to the maintenance of insulin sensitivity. Moreover, an increase in phosphorylation of glucose in adipose tissue could also lead to increased esterification of fatty acids and lipids deposit, through an increase in its procurement of glicerol-3-fosfato. Therefore, in the second part of this Doctoral Thesis, expressed the enzyme glucoquinasa (GK) in adipose tissue of mice, an enzyme regulating the use of glucose in the liver. The presence of GK on adipose tissue increased its basal glucose uptake, and improved glucose tolerance and insulin sensitivity in these animals. Despite the increased use of glucose in white adipose tissue, this does not generate more glicerol-3-fosfato or alter the deposit of lipids, but increased its production of lactate, increasing their levels circulates 8 nten. Po 59c r therefore, these results suggest that an increase in glucose uptake by adipose tissue does not lead to an increased synthesis of lipids but an increase in the production of lactate. All these results suggest that the regulation of input glicerol-3-fosfato contributes to the control of the synthesis of triglycerides. In addition, show the direct involvement of PEPCK in the synthesis of glicerol-3-fosfato and highlighted the key role of gliceroneogénesis in re-esterification of fatty acids and consequent accumulation of fat, both in brown and white adipose tissue. However, the increase in the uptake and utilization of glucose is not sufficient to promote the generation of glicerol-3-fosfato and storage of fat.

Author: SEBASTIAN MUÑOZ DAVID.
Year: 2005.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: DPTO. BIOQUÍMICA Y BIOLOGÍA MOLECULAR (FARMACIA).

Summary: Insulin resistance is a pathological condition which is defined as the body's inability to respond normally to the actions of insulin. Numerous studies have described the accumulation of species derived from fatty acids in muscle, either due to a contribution or an excessive lipid oxidation in his judgment, leading to a resistance to insulin. This thesis has been studied whether an increase in fatty acid oxidation in muscle is able to prevent the accumulation of lipid derivatives and thus avoid insulin resistance caused by them. It has been shown that overexpression of CPT I therefore of fatty acid oxidation, prevents accumulation and thus protects cell resistance to insulin. It has also shown that the C75 (described as a drug activator CPT R), through its activation to C75-CoA, behaves as an inhibitor of CPT I therefore of fatty acid oxidation in skeletal muscle . Lastly, has been unable to demonstrate that FAT/CD36 play an important role in fatty acid oxidation in a position to study utilized. These results confirm the importance of lipid metabolism in insulin resistance in muscle and the CPT I described as a possible drug target for treatment of insulin resistance and diabetes type 2. On the other hand describes a new action C75 on the CPT activity I suggest the need for further studies to clarify the role of FAT/CD36 in fatty acid oxidation in skeletal muscle.

Author: GARCÍA ESCOBAR EVA.
Year: 2006.
University: MÁLAGA [www.uma.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA - UNIVERSIAD DE MÁLAGA.

Summary: The study of the effects of dietary fatty acids on the metabolism adipocitario is of great interest to understand the pathophysiology in some high prevalence of diseases such as obesity, diabetes or hypertension. The problem is that in trying to work to clarify the role of the fatty acids is that it is very difficult to separate the effect of increasing the diet of a particular fatty acid, the decline of another in similar proportion to that is being investigated. This paper has studied lso effects, dose-dependent, oleic acid in the diet, in an experimental animal model in rats: 1-On the lipolisis in adipocitos cultured in vitro stimulated with espinerfrina and inhibited insulin. 2-About circulating levels of leptin, adiponectina and free fatty acids and on the levels of gene expression of some genes involved in the metabolism of fatty acids (SCD-1, PPARalfa, PPAR, PPARgamma, leptin and HSL). They also have studied the relationships of these variables with the fatty acid composition of the tissue, and between them. Having found, inter alia: * A dose-dependent response of the concentration of oleic acid in the diet on lipolisis stimulated adipocitos cultured in vitro. * Levels of expression of the genes studied are most affected by diet when studying in the adipose tissue, rather than muscle or liver. * Levels of expression of SCD1 differ depending on the concentration of oleic acid in the tissues and correlated inversely with the linoleic acid content of adipose tissue, fatty acid that is derived exclusively from the diet, and directly with the content saturated fatty acid.