Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection
induced obesity, slightly elevated fasting blood glucose and impaired glucose and
insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as
published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences
in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9)
or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four
(prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and
kidney and liver samples were collected for histology, immunohistochemistry and for
analysis of gene expression. HFD and STZ increased body weight and visceral adiposity
and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein
concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen
IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while
Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON
rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret
diameter, desmin protein expression, and cortical and medullary mRNA expression of
TGF-β1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation
of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid
and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition
and increased lipocalin-2 expression were the early signs of kidney injury, while
most biomarkers of inflammation, oxidative stress and fibrosis were negative in the
kidneys of obese, prediabetic rats with mild heart and liver injury.
