Tribolium castaneum (Coleóptera: Tenebrionidae) como modelo alternativo para estudo da Síndrome Metabólica

Abstract

Tribolium castaneum (Coleopter: Tenebrionidae), or red flour beetle, is considered one of the main secondary pests of grains, with worldwide distribution, being responsible for great economic losses. Some characteristics of this insect favor its use as a model in transgenerational, biochemical and genetic studies, such as rapid reproduction, high fertility, short generation intervals, low maintenance costs, ease in incorporating nutritional factors into the diet, acceptable ethical aspects, observable tissues and genome available. In addition, some insects such as T. castaneum, have a digestive process and lipid metabolism analogous to mammals, highlighting them as models for metabolic studies. Thus, this thesis aims to establish the insect T. castaneum as an alternative model of low cost and high effectiveness for the study of Metabolic Syndrome and drugs used in this dysfunction, giving it a biotechnological application through different approaches used in the five presented chapters. The first chapter is a theoretical overview of the main points addressed in this thesis. The second chapter consists of a technological survey that aimed to analyze patent applications and articles referring to the use of T. castaneum as an experimental model for studies in carbohydrate and lipid metabolism, noting that none of the analyzed applications refers to the object of this study, it is concluded that this is a technological area little explored and potentially useful for new research and products. Thus, the third chapter refers to the development of a new method of preparing these insects as an invertebrate model of low cost and high efficiency, for the study of the Metabolic Syndrome and the effect of candidate drugs in this dysfunction, as well as the application for patent protection of this method innovative. In affirming this applicability, the fourth chapter presents experimental results that aimed to analyze mitochondrial bioenergetic disorders, through the production of reactive oxygen species and the biochemical and metabolic changes caused by metabolic (in)flexibility. For this, T. castaneum larvae were kept on a diet rich in lipids for 168 hours and, later, transferred to a diet supplemented with 1% fenofibrate. It was identified that 15% olive oil induced hyperglycemia, hypertriglyceridemia, hypercholesterolemia and obesity, changes in Metabolic Syndrome, in addition to insulin resistance and greater generation of reactive oxygen species, with a consequent increase in mitochondrial respiration (complex II), such as compensatory mechanism. On the other hand, supplementation with fenofibrate restored metabolic disorders to a level close to that observed in the control group. Similarly, the last chapter presents an analysis of Bioinformatics, highlighting, among the insects, the emerging model T. castaneum as more appropriate to study the conserved function of miRs, since this insect has a mature sequence homologous to Homo sapiens (miR -33a) and, in phylogenetic analysis, it is evolutionarily closer to man when compared to drosophila, in addition to presenting target genes similar to miR-33 in humans. In this way, the five chapters surround the Metabolic Syndrome (through mitochondrial bioenergetics or miR-33) and use T. castanum as a low cost and high effectiveness model for research, envisioning this biotechnological applicability as a bioethical and economic alternative, which makes it possible to advance in research and achieve results that cause positive impacts and contribute to reducing the overall incidence of this dysfunction.