EpiOmics: a translational validation of the proteomic, biochemical and metabolic profile between mice and humans supplemented with epicatechin: implications of diet, gender and thermoneutrality

Abstract

Cerebrovascular and cardiovascular diseases, cancer, obesity, diabetes, hypertension, among others, collectively grouped in the category of chronic non-communicable diseases (NCDs), are today the main causes of morbidity and mortality worldwide. Nutrition and physical activity are considered non-invasive strategies of great impact, and the first choice to prevent and/or treat NCDs. Nutrigenomics and epigenetics are expanding research areas in biology and bring to light the interaction of food and environmental factors with the individual's genotype, thus modifying the phenotype. The WHO recommends that regular dietary intake of fruits, vegetables, grains and cereals, and a plant-based diet, associated with a reduction in ultra-processed foods, in addition to the practice of physical activity, in the long term, bring unique health benefits for individuals. Polyphenols are bioactives considered responsible for some of the health benefits provided by fruits and vegetables. Results already published by the group show that, among the green tea catechins (GT) investigated as potential PPAR transcription factor ligands, epicatechin (EC) presented the best performance and best results as a direct PPARg ligand. This data per se already justifies the research with EC isolated in an in vivo, in vitro and human model, in view of the importance of PPARg in obesity. Despite several results published by the group so far, we have not carried out a clinical trial, and it was not yet possible for us to assemble a complete picture of which pathways are activated and/or inhibited in obesity by polyphenols. Therefore, we have as main objective that guides this proposal the identification of the protein profile in the plasma of obese humans in parallel with obese and eutrophic mice - both species distinguished by the genus - and supplemented with epicatechin using proteomics technology. Furthermore, we intend to differentiate the proteomic, biochemical and metabolic profile in animals kept at two vivarium temperatures, 22°C and 28°C, with the aim of validating and comparing, if possible, with previous results to confirm whether the beneficial effects and VC thermogenics are preserved, lost or improved in thermoneutrality (28°C). Thermoneutrality was recently indicated as the best temperature for translating data from obese animals to humans. Another important aspect that this proposal intends to investigate is the possible metabolic contrast and severity of diet-induced obesity between males and females (gender-dependent effect), as recent studies indicate important metabolic differences between genders in obesity. The main hypothesis of the project is that EC supplementation will impact the plasma proteomic profile of obese humans, as well as the obese mouse model kept at 28°C, in order to produce proteomes that will enable the identification of biomarkers and metabolic maps. In common among the study groups, in addition to the expression of a more beneficial proteome induced by EC. The proteomic tool that we intend to use in this work may provide important insights into the understanding between cell signaling and the dynamics of gene and protein expression regulation, as well as the metabolic change, evidenced when obese animals are treated with polyphenols. Furthermore, as reported by several authors, we intend to confirm or refute whether the results in obese mice maintained in thermoneutrality can be translated to obese humans with proteomics as a background. (AU)