Tribolium castaneum como modelo para estudo de obesidade: efeitos de dietas hipercalóricas no metabolismo e fisiologia do inseto

Abstract

Obesity causes severe consequences to people's health, leading to diseases like type II diabetes, hypertension, and others. In Brazil, some predictions indicate that, by 2050, most of its population will be obese, and the expenses for treatments could reach hundreds of billions of dollars. The absence of effective, safe, and cheap drugs to treat obesity reduces the options to combat this disease. The similarities between the metabolic and signaling pathways in insects and mammals support using these arthropods as models to investigate this area. Furthermore, genomic and transcriptomic data and RNAi tool efficiency corroborate using the beetle Tribolium castaneum as an attractive model. This project aimed to investigate the effects of hypercaloric diets on the lipid metabolism of T. castaneum and to establish the beetle as a model to study obesity and type II diabetes. Larvae were fed wheat flour supplemented with various hypercaloric sources such as olive oil or egg yolk powder (high-fat diet), tryptone (high-protein diet), or sucrose or glucose (high-sugar diet). The amount of triacylglycerol (TAG), total sugar, glycogen, and trehalose was measured using a colorimetric assay, while ATP-citrate lyase (ACLY) activity was measured using a coupled enzymatic assay. Total lipids were extracted and analyzed by mass spectrometry. Gene expression was determined by quantitative PCR and RNAseq. Olive oil supplementation caused an increase in TAG in the whole body and delayed larval growth. Other hypercaloric diets were tested, but it was only possible to observe a significant increase in TAG with a 10% w/w tryptone diet. As for gene expression, a diet supplemented with olive oil increased levels of carnitine palmitoyltransferase 1 (CPT-1), a gene involved in beta-oxidation, and diacylglycerol acyltransferase (DGAT), a gene responsible for converting diacylglycerol into TAG. On the other hand, a high-protein diet decreased the expression of genes related to the lipid anabolic pathway, such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). The enzymatic activity of ACLY did not show any changes in larvae fed with protein. Moreover, transcriptomic data showed increased levels of genes related to cuticular processes. Glycogen levels increased in an olive oil-supplemented diet, while they decreased in a high-protein diet. These results indicate that hypercaloric diets induce phenotypes similar to obesity and diabetes in T. castaneum. However, further investigations are needed to confirm this beetle as a model to study metabolic diseases.