Efeitos da linagliptina no tecido adiposo branco subcutâneo de camundongos obesos: browning e termogênese associada

Abstract

The present study aimed to investigate linagliptin (DPP-4i) remodeling effects on subcutaneous white adipose tissue (sWAT), regarding thermogenesis and browning induction, on a murine diet-induced obesity model. Methods: Forty adult animals (C57BL/6) were randomly assigned to receive a control diet (C, 10% lipids as energy, n=20) or a high-fat diet (HF, 50% lipids as energy, n=20) for ten weeks. After, each group was re-divided to begin the five-week treatment, totalizing four experimental groups: C, C-L (C plus linagliptin, 30mg/kg body mass), HF and HF-L (HF plus linagliptin 30mg/kg BM). The drug was mixed with diet. Data from food behavior, indirect calorimetry and termography were colected and oral glucose tolerance test, plasmatic levels of insulin, light and immunofluorescence microscopy and gene expression were evaluated. Results: HF animals showed overweight, glucose intolerance, and greater cross-sectional area of adipocytes. The treatment with linagliptin was able to normalize the body mass (BM), restore the glucose tolerance and the cross-sectional area of adipocytes. These observations comply with the observation of UCP1 positive multilocular adipocytes in the subcutaneous white adipose tissue (sWAT) of treated animals. Both treated groups (C-L and HF-L) showed high expression of thermogenic genes, which agree with the enhanced body temperature (BT) and the lower respiratory exchange ratio (RER), implying enhanced thermogenesis with the use of lipids as fuel. Conclusion: The reduced BM, the enhanced BT and the presence of positive UCP1 beige cells in the sWAT point to the activation of the browning cascade on the sWAT of linagliptin-treated mice, and hence, linagliptin could induce the thermogenic pathway as a pleiotropic effect that can have translational potential