Glomerular collagen deposition and lipocalin-2 expression are early signs of renal injury in prediabetic obese rats

Eva Nora Bukosza, Tamás Kaucsár, Mária Godó, Enikő Lajtár, Pál Tod, Gábor Koncsos, Zoltán V. Varga, Tamás Baranyai, Nguyen Minh Tu, Helga Schachner, Csaba Sőti, Péter Ferdinandy, Zoltán Giricz, Gábor Szénási, Péter Hamar

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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.

Original languageEnglish
Article number4266
JournalInternational journal of molecular sciences
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2019

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Keywords

  • Collagen type IV
  • Inflammation
  • Lipocalin-2
  • Obesity
  • Renal injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Bukosza, E. N., Kaucsár, T., Godó, M., Lajtár, E., Tod, P., Koncsos, G., Varga, Z. V., Baranyai, T., Tu, N. M., Schachner, H., Sőti, C., Ferdinandy, P., Giricz, Z., Szénási, G., & Hamar, P. (2019). Glomerular collagen deposition and lipocalin-2 expression are early signs of renal injury in prediabetic obese rats. International journal of molecular sciences, 20(17), [4266]. https://doi.org/10.3390/ijms20174266