Abstract
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.
Highlights
Obesity has a worldwide epidemic with a rapidly increasing incidence affecting more than 600 million patients [1]
The burden of obesity is magnified by the various secondary diseases that can develop in obese individuals e.g.,: Non-alcoholic steatohepatitis [2], heart failure with preserved ejection fraction [3], as well as obesity-related glomerulopathy [4,5,6,7]
Cholesterol, low density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were similar in the groups (Figure 2A–D)
Summary
Obesity has a worldwide epidemic with a rapidly increasing incidence affecting more than 600 million patients [1]. The burden of obesity is magnified by the various secondary diseases that can develop in obese individuals e.g.,: Non-alcoholic steatohepatitis [2], heart failure with preserved ejection fraction [3], as well as obesity-related glomerulopathy [4,5,6,7] It is unpredictable which disease will develop in a particular patient, and it is unknown how long the obese state lasts before the first co-morbidity symptoms appear in a patient. The aim of the current study was to explore the renal consequences of obesity and prediabetic state in a part of the same rats, in order to reveal early markers of obesity-related renal end-organ damage
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