Journal
NUTRIENTS
Volume 12, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/nu12040881
Keywords
prediabetes; nephropathy; rat model; diet-induced; renal lipidosis; glomerular crescent-like lesions
Categories
Funding
- European Regional Development Fund (FEDER), through Programa Operacional Factores de Competitividade COMPETE2020 [CENTRO-01-0145-FEDER-000012-HealthyAging2020]
- Portuguese Science and Technology Foundation (FCT) [UID/NEU/04539/2013, UID/NEU/04539/2019, UIDB/04539/2020, UIDP/04539/2020, SFRH/BD/109017/2015, PTDC/SAU-NUT/31712/2017]
- COMPETE-FEDER funds [POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-031712]
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Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.
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