Influence of PPARG in glycemic and immune alterations related with Type 2 Diabetes Mellitus and Periodontitis

Abstract

It has been increasingly common to find patients affected by the combination of Type 2 Diabetes Mellitus (DM2), Dyslipidemia and Periodontitis (P). There is also growing evidence in the literature demonstrating interactions between DM2, Dyslipidemia, immune system dysfunction and Periodontitis. For a better understanding of such interactions, studies with animal models, mainly murine, have been valuable. However, more clinical studies with patients, as well as with murine models, are needed to know molecules with a key role in the interaction between glycemic and lipid metabolism and the immune system, in addition to better understanding the interaction between the individual's oral and systemic health. The role of the Receptor Activated by Peroxisome Gamma Proliferator (PPAR-³) in the regulation of glycemic, lipid and immune system metabolism is known, but there are few studies that investigate its action in the modulation of DM2 and Periodontitis. Indicators from the literature and our previous results (with patients) support our hypothesis that PPAR-³, employing TNF- ± is a key molecule for these pathologies. The general objective of this study is to perform the functional morpho-evaluation of PPAR-³ as a key molecule for glycemic and immunological changes in DM2 and Periodontitis, occurring as comorbidities, or in isolation. Murine model methodology: 48 male C57BL/6J mice will be evaluated in each group: DM, Periodontitis, DM + P, and Control. DM will be induced by the combination of high-fat diet and streptozotocin injection; and Periodontitis will be induced by a combination of ligation and infection by Porphyromonas gingivalis. Twelve animals in each group will be euthanized in the experimental periods Zero, 7, 14 and 21 days of treatment. Periodontal bone loss in animals will be assessed by micro-CT. The behavior of key PPAR-³ molecules, in addition to TNF- ±, TGF-²1 and IL-10, will be evaluated in all groups and periods through (i) morphology (histological and stereometric, focusing mainly on inflammatory aspects) and immunohistochemistry of collected gingival tissue, for localization and quantification of these proteins; (ii) functional evaluation by quantifying systemic transcriptional levels (mRNA in murine blood), systemic translational levels (protein levels in murine blood), in addition to periodontal transcription (murine gingiva mRNA) and translational (murine gingiva immunohistochemistry). Linear and/or multiple logistic regressions will be performed, in addition to correlation analyzes, of the transcriptional and translational levels of these molecules depending on the glycemic, lipid and periodontal profiles, intra- and inter-groups in the different periods. Through this clinical study and with a murine model, we will deepen the understanding of the pathogenic interaction between DM2 and Periodontitis. This will contribute to biomedicine and biotechnology to identify biomarkers for diagnosis and clinical monitoring of DM2 and Periodontitis. (AU)