Metabolic effects of interesterified fat and its metabolites on glucose and lipid homeostasis

Abstract

During the last decades, studies of different dietary fatty acids have been carried out to understand the effect of fat intake on risk markers for obesity and associated disease. The overconsumption of dietary fats leads to diet-induced activation of inflammatory pathways which is implicated in driving aspects of metabolic dysfunction, including the development of obesity and insulin resistance (IR). Increased concentrations of harmful lipid intermediates and final products, such as ceramides, can lead to lipotoxicity, which impairs cell homeostasis and disrupts tissue function. Although the evidence demonstrates an association between fat intake and the development of IR, the molecular mechanisms of nutrients triggering IR, particularly the different types of lipids (triacylglycerols and fatty acids) in a diet are still poorly understood. Triacylglycerols (TAGs) are the major form of dietary lipids, however, little is known about the biological and nutritional importance of the stereospecific compositions of TAGs. The TAG structure consists of a glycerol backbone esterified in distinct patterns with three fatty acids (FAs), in stereospecific positions in the glycerol (sn-1, sn-2 and sn-3). The type of FA, the chain length of the FAs, the degree of saturation and their configuration (cis or trans), and its stereospecificity in the TAG, determine the physical behavior and biochemical properties of dietary fats, influencing absorption, metabolism and tissue uptake. Dietary TAGs occur naturally or they can be also manufactured from vegetable oils and/or animal fats by modifying the chain of FAs by partially hydrogenation process, generating trans fats, or they can also alter the FAs positions in the TAGs, by interesterification. The interesterified fats have been used as a substitute to trans fat, this process supplies fats with the functional properties required by the food manufacturers, however, few studies have assessed the role of interesterified fats in the metabolism and whether or not interesterification may adversely affect the metabolism. Thus, the effects of interesterified fat on metabolism require further investigation and it remains to be determined whether the effects of interesterified fats on metabolism is as deleterious as trans fat. In this context, it becomes a matter of priority to study the effects of the interesterified fat and to understand the molecular mechanisms induced by these modified fats on glucose homeostasis and lipid metabolism. For this purpose, we intended expand our knowledge in the research of interesterified fat and bring new methodological approaches to contribute to the development and improvement of techniques that will add to our scientific and academic environment. Innovative techniques will be imported and improved, especially regarding the assessment of glucose homeostasis, by means of a euglycemic hyperinsulinemic clamp, lipid metabolism by lipidomic analysis and lipid signaling and its effects in the central nervous system by intracarotid lipid infusion technique.