P0997BLUEBERRY JUICE IMPROVED THE METABOLIC PROFILE IN A PREDIABETIC RAT MODEL INDUCED BY A HYPERCALORIC DIET WITHOUT RENOPROTECTION

Abstract

Abstract Background and Aims Blueberries (BB), due to their enriched content in polyphenolics and in other compounds with potential cytoprotective properties, have been associated with beneficial effects in distinct cardiometabolic conditions. The goal of this study was to evaluate the metabolic and renal effects of long-term blueberry juice (BJ) treatment in a rat model of prediabetes induced by a hypercaloric diet. Method Prediabetes was developed in adult male Wistar rats through the ingestion of high-sucrose (35% HSu) and high-fat (60% HF) diets during 23 wks (HSuHF animals, n=16). After 9 weeks, half of the former rats received BJ orally (25g/kg BW, HSuHF+BJ group). Control animals (n=8) received standard diet during the entire protocol. Glycemic, lipidic and insulinemic profiles were evaluated throughout the protocol, as well as gut microbiota composition, gut barrier permeability, endotoxemia (LPS) and inflammation (hs-CRP). Renal function was assessed by using serum and urinary measures of creatinine, uric acid and blood urea nitrogen and calculating the glomerular filtration rate (GFR). Histological characterization of the kidney was performed by H&E and lipid deposition by Oil Red O staining and quantification of triglycerides. Serum and renal tissue inflammatory markers were evaluated by Elisa (hs-CRP) and by RT-qPCR and/or WB (IL-6, TNF-α, iNOS, MMP2, TLR-4 and RAGE). The study was approved by the local animal welfare body (Ref: 9-2018). Values are presented as means ± S.E.M. and possible differences evaluated by ANOVA/post-hoc tests. Results While no major changes between groups were found for gut microbiota, gut barrier and endotoxemia/inflammation, BJ treatment was able to ameliorate hypercaloric diet-induced glucose intolerance, insulin insensitivity and plasma hypertriglyceridemia. In addition, in the HSuHF+BJ rats there was a trend to alleviate the reduction of GFR found in the HSuHF animals, as well as some early glomerular lesions, including mesangial expansion and basal membrane thickening. However, this nutraceutical intervention was unable to halt or slow down glomerular crescent-like lesions, renal lipidosis and the overexpression of renal IL-6 found in the HSuHF-treated animals. Conclusion Despite the metabolic improvement viewed by the amelioration of glucose intolerance, insulin insensitivity and hypertriglyceridemia, in this rat model of prediabetes a nutraceutical intervention with BJ presented very modest renoprotective effects. Acknowledgements: FEDER, COMPETE and FCT (CENTRO-01-0145-FEDER-000012-HealthyAging2020, UID/NEU/04539/2013, UID/NEU/04539/2019, POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-031712, PTDC/SAU-NUT/31712/2017 and SFRH/BD/109017/2015), as well as COAPE and MIRTILUSA.