Dietary DHA/EPA supplementation ameliorates diabetic nephropathy by protecting from distal tubular cell damage

  • Marija Vitlov Uljević
  • Kristina Starčević
  • Tomislav Mašek
  • Ivana Bočina
  • Ivana Restović
  • Nives Kević
  • Anita Racetin
  • Genia Kretzschmar
  • Maximilian Grobe
  • Katarina Vukojević
  • Mirna Saraga-Babić
  • Natalija FilipovićEmail author
Regular Article


The aim was to explore the influence of experimental diabetes mellitus type 1 (DM1) and potential protective/deleterious effects of different dietary n−6/n−3 PUFA ratios on renal phospholipid composition and pathological changes caused by DM1. Male Wistar rats were injected with 55 mg/kg streptozotocin or citrate buffer (control group). Control (C) and diabetic groups (STZ) were fed with n−6/n−3 ratio of ≈ 7, STZ + N6 with n−6/n−3 ratio ≈ 60 and STZ + DHA with n−6/n−3 ratio of ≈ 1 containing 16% EPA and 19% DHA. Tissues were harvested 30 days after DM1 induction. Blood and kidneys were collected and analysed for phospholipid fatty acid composition, pathohystological changes, ectopic lipid accumulation and expression of VEGF, NF-kB and special AT-rich sequence-binding protein-1 (SATB1). Pathological changes were studied also by using transmission electron microscopy, after immunostaining for VEGF. Substantial changes in renal phospholipid fatty acid composition resulted from DM1 and dietary PUFA manipulation. Extensive vacuolization of distal tubular cells (DTCs) was found in DM1, but it was attenuated in the STZ + DHA group, in which the highest renal NF-kB expression was observed. The ectopic lipid accumulation was observed in proximal tubular cells (PTCs) of all diabetic animals, but it was worsened in the STZ + N6 group. In DM1, we found disturbance of VEGF-transporting vesicular PTCs system, which was substantially worsened in STZ + DHA and STZ + N6. Results have shown that the early phase of DN is characterized with extent damage and vacuolization of DTCs, which could be attenuated by DHA/EPA supplementation. We concluded that dietary fatty acid composition can strongly influence the outcomes of DN.


Diabetic nephropathy PUFA Distal tubules SATB1 VEGF 



This work has been supported in part by the Croatian Science Foundation under the projects (IP-2014-09-8992; T. Mašek and 3163; K. Starčević) and by the Ministry of Science, Education and Sports of the Republic of Croatia (I. Bočina, K. Vukojević, N. Filipović).

Compliance with ethical statements

Conflict of interest

On behalf of all the authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All experimental protocols were approved by the National Ethics Committee (EP 13/2015) and Veterinary Directorate, Ministry of Agriculture, Republic of Croatia and conducted according to the Croatian Animal Welfare Act.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Marija Vitlov Uljević
    • 1
  • Kristina Starčević
    • 2
  • Tomislav Mašek
    • 3
  • Ivana Bočina
    • 4
  • Ivana Restović
    • 5
  • Nives Kević
    • 4
  • Anita Racetin
    • 6
  • Genia Kretzschmar
    • 1
  • Maximilian Grobe
    • 1
  • Katarina Vukojević
    • 1
    • 6
  • Mirna Saraga-Babić
    • 6
  • Natalija Filipović
    • 1
    Email author
  1. 1.Department of Anatomy, Histology and Embryology, Laboratory for NeurocardiologyUniversity of Split School of MedicineSplitCroatia
  2. 2.Department for Forensic and State Veterinary Medicine, Laboratory for Forensic Molecular BiologyUniversity of Zagreb Faculty of Veterinary MedicineZagrebCroatia
  3. 3.Department of Animal Nutrition and DieteticsUniversity of Zagreb Faculty of Veterinary MedicineZagrebCroatia
  4. 4.Department of BiologyUniversity of Split Faculty of ScienceSplitCroatia
  5. 5.Department of Teacher EducationUniversity of Split Faculty of PhilosophySplitCroatia
  6. 6.Department of Anatomy, Histology and Embryology, Laboratory for Early Human DevelopmentUniversity of Split School of MedicineSplitCroatia

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