Functional and morphological renal changes in a Göttingen Minipig model of obesity-related and diabetic nephropathy

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  • Berit Østergaard Christoffersen
  • Camilla Aarup Kristensen
  • Rikke Lindgaard
  • Rikke Kaae Kirk
  • Birgitte Martine Viuff
  • Peter Helding Kvist
  • Henrik Duelund Pedersen
  • Trine Pagh Ludvigsen
  • Tine Skovgaard
  • Johannes Josef Fels
  • Martinussen, Torben
  • Liselotte Bruun Christiansen
  • Cirera, Susanna
  • Olsen, Lisbeth Høier

Obesity-related glomerulopathy and diabetic nephropathy (DN) are serious complications to metabolic syndrome and diabetes. The purpose was to study effects of a fat, fructose and cholesterol-rich (FFC) diet with and without salt in order to induce hypertension on kidney function and morphology in Göttingen Minipigs with and without diabetes. Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n = 8), FFC (FFC diet, n = 16), FFC-DIA (FFC diet + diabetes, n = 14), FFC-DIA + S (FFC diet with extra salt + diabetes, n = 14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure (BP) and resistive index (RI) were evaluated after 6-7 months (T1) and 12-13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA + S) were evaluated at T2. All groups fed FFC-diet displayed obesity, increased GFR and RI, glomerulomegaly, mesangial expansion (ME) and glomerular basement membrane (GBM) thickening. Diabetes on top of FFC diet led to increased plasma glucose and urea and proteinuria and tended to exacerbate the glomerulomegaly, ME and GBM thickening. Four genes (CDKN1A, NPHS2, ACE, SLC2A1) were significantly deregulated in FFC and/or FFC-DIA compared to SD. No effects on BP were observed. Göttingen Minipigs fed FFC diet displayed some of the renal early changes seen in human obesity. Presence of diabetes on top of FFC diet exacerbated the findings and lead to changes resembling the early phases of human DN.

Original languageEnglish
Article number6017
JournalScientific Reports
Number of pages13
Publication statusPublished - 2023

Bibliographical note

© 2023. The Author(s).

    Research areas

  • Animals, Swine, Male, Humans, Diabetic Nephropathies/pathology, Swine, Miniature, Kidney/pathology, Obesity/pathology, Glomerular Basement Membrane/pathology, Diabetes Mellitus/pathology

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