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

被引：2

作者：

Christoffersen, Berit Ostergaard ^{[1
]}

Kristensen, Camilla Aarup ^{[2
,4
]}

Lindgaard, Rikke ^{[1
,2
,5
]}

Kirk, Rikke Kaae ^{[1
]}

Viuff, Birgitte Martine ^{[1
]}

Kvist, Peter Helding ^{[1
]}

Pedersen, Henrik Duelund ^{[1
,6
]}

Ludvigsen, Trine Pagh ^{[1
]}

Skovgaard, Tine ^{[1
,7
]}

Fels, Johannes Josef ^{[1
]}

Martinussen, Torben ^{[3
]}

Christiansen, Liselotte Bruun ^{[2
,8
]}

Cirera, Susanna ^{[2
]}

Olsen, Lisbeth Hoier ^{[2
]}

机构：

[1] Novo Nordisk AS, Malov, Denmark

[2] Univ Copenhagen, Dept Vet & Anim Sci, Frederiksberg, Denmark

[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark

[4] AJ Vaccines AS, Copenhagen, Denmark

[5] AniCura ApS, Herlev, Denmark

[6] Danish Med Agcy, Copenhagen, Denmark

[7] Unilabs, Copenhagen, Denmark

[8] Novo Nordisk AS, Soborg, Denmark

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

BLOOD-PRESSURE; METABOLIC SYNDROME; RESISTIVE INDEX; KIDNEY; SALT; DIET; HYPERTENSION; EXPRESSION; RESISTANCE; MELLITUS;

D O I：

10.1038/s41598-023-32674-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Gottingen Minipigs with and without diabetes. Male Gottingen 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. Gottingen 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.

引用

页数：13

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[1] The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy [J].