TY - JOUR

T1 - Functional and morphological renal changes in a Göttingen Minipig model of obesity-related and diabetic nephropathy

AU - Christoffersen, Berit Østergaard

AU - Kristensen, Camilla Aarup

AU - Lindgaard, Rikke

AU - Kirk, Rikke Kaae

AU - Viuff, Birgitte Martine

AU - Kvist, Peter Helding

AU - Pedersen, Henrik Duelund

AU - Ludvigsen, Trine Pagh

AU - Skovgaard, Tine

AU - Fels, Johannes Josef

AU - Martinussen, Torben

AU - Christiansen, Liselotte Bruun

AU - Cirera, Susanna

AU - Olsen, Lisbeth Høier

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Animals

KW - Swine

KW - Male

KW - Humans

KW - Diabetic Nephropathies/pathology

KW - Swine, Miniature

KW - Kidney/pathology

KW - Obesity/pathology

KW - Glomerular Basement Membrane/pathology

KW - Diabetes Mellitus/pathology

U2 - 10.1038/s41598-023-32674-6

DO - 10.1038/s41598-023-32674-6

M3 - Journal article

C2 - 37045950

VL - 13

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 6017

ER -