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Article: Dietary normalization from a fat, fructose and cholesterol-rich diet to chow limits the amount of myocardial collagen in a Göttingen Minipig model of obesity

Olsen, Lisbeth Høier

Nutrition & metabolism, 15:64

2018

Abstract: BACKGROUND: Dietary interventions have been shown to attenuate some of the myocardial pathological alterations associated with obesity. This study evaluated the effect of dietary normalization from a fat/fructose/cholesterol-rich diet to chow on left ... ...

Abstract	BACKGROUND: Dietary interventions have been shown to attenuate some of the myocardial pathological alterations associated with obesity. This study evaluated the effect of dietary normalization from a fat/fructose/cholesterol-rich diet to chow on left ventricular (LV) myocardial fibrosis, fat infiltration and hypertrophy but also the specific influence of obesity, plasma lipids and glucose metabolism markers on heart morphology in a Göttingen Minipig model of obesity. METHODS: Forty castrated male Göttingen Minipigs were assigned to three groups fed either standard minipig chow (SD, n = 8) for 13 months, fat/fructose/cholesterol-rich diet (FFC, n = 16) for 13 months or fat/fructose/cholesterol-rich diet for 7 months and then changed to standard minipig chow for the remaining 6 months (FFC/SD, n = 16). Body weight, body fat percentage, plasma lipids and glucose metabolism markers were evaluated in all three groups after 6–7 months (prior to diet adjustment for FFC/SD) and again before termination. Further, biochemical quantification of myocardial collagen and triglyceride content, semi-quantitative histological evaluation of fibrosis and fat infiltration and quantitative histological analysis of collagen and cardiomyocyte diameter were performed and heart weight was obtained after termination. Group differences were evaluated using Kruskal-Wallis test and Fisher’s exact test for categorical variables. Pearson correlation analysis was performed to test for correlations between myocardial changes and selected explanatory variables. For non-parametric response variables, a Spearman correlation analysis was applied. RESULTS: Myocardial collagen content quantified biochemically was significantly lower in FFC/SD compared to FFC (P = 0.02). Furthermore, dietary normalization from a fat/fructose/cholesterol-rich diet to chow caused stagnation of body weight and body fat percentage, normalized intravenous glucose tolerance index (KG) and plasma lipid levels. CONCLUSION: Dietary normalization led to lower LV collagen content in obese Göttingen Minipigs. Despite gross obesity and significant deteriorations in glucose and lipid metabolism, only mild myocardial changes were found in this model of obesity and therefore further model optimization is warranted in order to induce more severe myocardial changes before dietary or pharmacological interventions.
Keywords	Collagen ; Cardiomyocyte hypertrophy ; Dietary intervention ; Hydroxyproline ; Obesity ; Left ventricular remodeling ; Porcine model
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article: Implantation of telemetric blood pressure transmitters in Göttingen Minipigs: Validation of 24-h systemic blood pressure and heart rate monitoring and influence of anaesthesia

Carlsen, Michelle Fischer / Christoffersen, Berit Østergaard / Lindgaard, Rikke / Pedersen, Henrik Duelund / Olsen, Lisbeth Høier

Journal of pharmacological and toxicological methods. 2022 May, June, v. 115

2022

Abstract: Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen Minipigs, and in ... ...

Abstract	Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen Minipigs, and in addition to study the effects of three different anaesthesia protocols on telemetric BP and HR measurements. Eight female Göttingen Minipigs had telemetry transmitters implanted in the right carotid artery. Over ten weeks, systemic 24-h BP and HR monitoring were repeated four times, each ending with an angiotensin II stimulation test. In addition, systemic BP and HR evaluated by telemetry, intra-arterial catheter (IAC) and oscillometric tail-cuff were compared before and after the 10-weeks period. Furthermore, changes in telemetric systemic BP and HR were monitored during anaesthesia in a cross-over design using three different protocols of general anaesthesia: Midazolam/ketamine (MK), propofol, and a combination of tiletamine, zolazepam, xylazine, ketamine and butorphanol (Zoletil-mix). One minipig was excluded and some data were missing due to central-venous catheter issues. The coefficient of variation was below 10% for the 24-h BP and HR measurements, but higher during angiotensin II stimulation. There was a disagreement between the tail-cuff measurement and telemetry/IAC, however the differences were independent of the BP and HR level. All anaesthesia protocols numerically influenced BP and HR, but only propofol statistically significantly decreased the BP. The study showed acceptable reproducibility of telemetric measurement of BP and HR over ten weeks in freely moving Göttingen Minipigs. There was a disagreement between direct and indirect BP measurement, and BP and HR were influenced by all anaesthesia protocols.
Keywords	anesthesia ; biomedical research ; blood pressure ; butorphanol ; carotid arteries ; central venous catheters ; cross-over studies ; females ; heart rate ; humans ; ketamine ; miniature swine ; swine ; telemetry ; tiletamine ; toxicology ; xylazine
Language	English
Dates of publication	2022-05
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2022.107168
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Implantation of telemetric blood pressure transmitters in Göttingen Minipigs: Validation of 24-h systemic blood pressure and heart rate monitoring and influence of anaesthesia.

Carlsen, Michelle Fischer / Christoffersen, Berit Østergaard / Lindgaard, Rikke / Pedersen, Henrik Duelund / Olsen, Lisbeth Høier

Journal of pharmacological and toxicological methods

2022 Volume 115, Page(s) 107168

Abstract: Introduction: Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen ... ...

Abstract	Introduction: Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen Minipigs, and in addition to study the effects of three different anaesthesia protocols on telemetric BP and HR measurements. Methods: Eight female Göttingen Minipigs had telemetry transmitters implanted in the right carotid artery. Over ten weeks, systemic 24-h BP and HR monitoring were repeated four times, each ending with an angiotensin II stimulation test. In addition, systemic BP and HR evaluated by telemetry, intra-arterial catheter (IAC) and oscillometric tail-cuff were compared before and after the 10-weeks period. Furthermore, changes in telemetric systemic BP and HR were monitored during anaesthesia in a cross-over design using three different protocols of general anaesthesia: Midazolam/ketamine (MK), propofol, and a combination of tiletamine, zolazepam, xylazine, ketamine and butorphanol (Zoletil-mix). Results: One minipig was excluded and some data were missing due to central-venous catheter issues. The coefficient of variation was below 10% for the 24-h BP and HR measurements, but higher during angiotensin II stimulation. There was a disagreement between the tail-cuff measurement and telemetry/IAC, however the differences were independent of the BP and HR level. All anaesthesia protocols numerically influenced BP and HR, but only propofol statistically significantly decreased the BP. Conclusion: The study showed acceptable reproducibility of telemetric measurement of BP and HR over ten weeks in freely moving Göttingen Minipigs. There was a disagreement between direct and indirect BP measurement, and BP and HR were influenced by all anaesthesia protocols.
MeSH term(s)	Anesthesia ; Angiotensin II ; Animals ; Blood Pressure ; Female ; Heart Rate ; Humans ; Ketamine/pharmacology ; Propofol/pharmacology ; Reproducibility of Results ; Swine ; Swine, Miniature ; Telemetry/methods
Chemical Substances	Angiotensin II (11128-99-7) ; Ketamine (690G0D6V8H) ; Propofol (YI7VU623SF)
Language	English
Publishing date	2022-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2022.107168
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Article: Electrocardiography and heart rate variability in Göttingen Minipigs: Impact of diurnal variation, lead placement, repeatability and streptozotocin-induced diabetes

Lyhne, Mille Kronborg / Debes, Karina Poulsdóttir / Helgogaard, Terese / Vegge, Andreas / Kildegaard, Jonas / Pedersen-Bjergaard, Ulrik / Olsen, Lisbeth Høier

Journal of pharmacological and toxicological methods. 2022 Nov., Dec., v. 118

2022

Abstract: The Göttingen Minipig is widely used in preclinical research and safety pharmacology, but standardisation of porcine electrocardiography (ECG) is lacking. The aim of this study was to investigate diurnal effects, change over time and choice of lead on ... ...

Abstract	The Göttingen Minipig is widely used in preclinical research and safety pharmacology, but standardisation of porcine electrocardiography (ECG) is lacking. The aim of this study was to investigate diurnal effects, change over time and choice of lead on ECG morphology and heart rate variability (HRV) in healthy and streptozotocin (STZ) induced diabetic Göttingen Minipigs. Diabetes was experimentally induced using STZ in 11 Göttingen Minipigs (DIA). Seven controls (CON) were included. 24-h ECG was recorded at baseline and four months. Morphological parameters (QRS and T wave duration, P- and T-wave amplitude, PR and QT (Bazett's (QTcb) or Fridericia (QTcf) correction) intervals and ST segment), presence of cardiac arrhythmias, heart rate (HR) and HRV (time and frequency domain) were analysed. Four months after induction, DIA had decreased P-wave amplitude (P < 0.0001) and T-wave duration (P = 0.017), compared to CON. QTcb was lower in DIA, but not in CON. Both groups had decreased HR (P < 0.0001) and QRS duration (lead II, P = 0.04) and length of PR-segment increased (lead I and II, P < 0.01) while selected HRV parameters also increased (all P < 0.01). Time of day influenced HR, QRS duration, PR segment, ST segment, T- and P-wave amplitude and some parameters of HRV. Inter- and intra-observer variability of morphological measurements was low (<6%). ECG parameters were influenced by time setting, diurnal variation and lead. Some ECG and HRV changes were found in diabetic minipigs four months after STZ induction. The findings underline the need for standardisation of ECG and HRV in Göttingen Minipigs.
Keywords	diabetes ; diurnal variation ; electrocardiography ; heart rate ; lead ; miniature swine ; pharmacology ; streptozotocin ; swine ; toxicology
Language	English
Dates of publication	2022-11
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2022.107221
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Article ; Online: Electrocardiography and heart rate variability in Göttingen Minipigs: Impact of diurnal variation, lead placement, repeatability and streptozotocin-induced diabetes.

Lyhne, Mille Kronborg / Debes, Karina Poulsdóttir / Helgogaard, Terese / Vegge, Andreas / Kildegaard, Jonas / Pedersen-Bjergaard, Ulrik / Olsen, Lisbeth Høier

Journal of pharmacological and toxicological methods

2022 Volume 118, Page(s) 107221

Abstract: Background: The Göttingen Minipig is widely used in preclinical research and safety pharmacology, but standardisation of porcine electrocardiography (ECG) is lacking. The aim of this study was to investigate diurnal effects, change over time and choice ... ...

Abstract	Background: The Göttingen Minipig is widely used in preclinical research and safety pharmacology, but standardisation of porcine electrocardiography (ECG) is lacking. The aim of this study was to investigate diurnal effects, change over time and choice of lead on ECG morphology and heart rate variability (HRV) in healthy and streptozotocin (STZ) induced diabetic Göttingen Minipigs. Methods: Diabetes was experimentally induced using STZ in 11 Göttingen Minipigs (DIA). Seven controls (CON) were included. 24-h ECG was recorded at baseline and four months. Morphological parameters (QRS and T wave duration, P- and T-wave amplitude, PR and QT (Bazett's (QTcb) or Fridericia (QTcf) correction) intervals and ST segment), presence of cardiac arrhythmias, heart rate (HR) and HRV (time and frequency domain) were analysed. Results: Four months after induction, DIA had decreased P-wave amplitude (P < 0.0001) and T-wave duration (P = 0.017), compared to CON. QTcb was lower in DIA, but not in CON. Both groups had decreased HR (P < 0.0001) and QRS duration (lead II, P = 0.04) and length of PR-segment increased (lead I and II, P < 0.01) while selected HRV parameters also increased (all P < 0.01). Time of day influenced HR, QRS duration, PR segment, ST segment, T- and P-wave amplitude and some parameters of HRV. Inter- and intra-observer variability of morphological measurements was low (<6%). Conclusion: ECG parameters were influenced by time setting, diurnal variation and lead. Some ECG and HRV changes were found in diabetic minipigs four months after STZ induction. The findings underline the need for standardisation of ECG and HRV in Göttingen Minipigs.
MeSH term(s)	Animals ; Swine ; Heart Rate ; Swine, Miniature ; Streptozocin ; Electrocardiography ; Arrhythmias, Cardiac/chemically induced ; Diabetes Mellitus
Chemical Substances	Streptozocin (5W494URQ81)
Language	English
Publishing date	2022-09-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1105919-9
ISSN	1873-488X ; 1056-8719
ISSN (online)	1873-488X
ISSN	1056-8719
DOI	10.1016/j.vascn.2022.107221
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Article ; Online: Cardiac adaptation in hibernating, free-ranging Scandinavian Brown Bears (Ursus arctos).

Jørgensen, Peter Godsk / Evans, Alina / Kindberg, Jonas / Olsen, Lisbeth Høier / Galatius, Søren / Fröbert, Ole

Scientific reports

2020 Volume 10, Issue 1, Page(s) 247

Abstract: During six months of annual hibernation, the brown bear undergoes unique physiological changes to adapt to decreased metabolic rate. We compared cardiac structural and functional measures of hibernating and active bears using comprehensive ... ...

Abstract	During six months of annual hibernation, the brown bear undergoes unique physiological changes to adapt to decreased metabolic rate. We compared cardiac structural and functional measures of hibernating and active bears using comprehensive echocardiography. We performed echocardiography on 13 subadult free-ranging, anaesthetised Scandinavian brown bears (Ursus arctos) during late hibernation and in early summer. Mean heart rate was 26 beats per minute (standard deviation (SD): 8) during hibernation vs 71 (SD: 14) during active state. All left ventricular (LV) systolic and diastolic measures were decreased during hibernation: mean ejection fraction: 44.2% (SD: 6.0) active state vs 34.0 (SD: 8.1) hibernation, P = 0.001; global longitudinal strain: -11.2% (SD: 2.0) vs -8.8 (SD: 3.3), P = 0.03; global longitudinal strain rate: -0.82 (SD: 0.15) vs -0.41 (SD: 0.18), P < 0.001; septal e': 9.8 cm/s (SD: 1.8) vs 5.2 (SD: 2.7), P < 0.001. In general, measures of total myocardial motion (ejection fraction and global longitudinal strain) were decreased to a lesser extent than measures of myocardial velocities. In the hibernating brown bear, cardiac adaptation included decreased functional measures, primarily measures of myocardial velocities, but was not associated with cardiac atrophy. Understanding the mechanisms of these adaptations could provide pathophysiological insight of human pathological conditions such as heart failure.
MeSH term(s)	Adaptation, Physiological ; Animals ; Electrocardiography ; Heart/physiology ; Hibernation/physiology ; Ursidae/physiology
Language	English
Publishing date	2020-01-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-57126-y
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Article ; Online: Nanopore sequencing reveals methylation changes associated with obesity in circulating cell-free DNA from Göttingen Minipigs.

Drag, Markus Hodal / Debes, Karina Poulsdóttir / Franck, Clara Sandkamm / Flethøj, Mette / Lyhne, Mille Kronborg / Møller, Jacob Eifer / Ludvigsen, Trine Pagh / Jespersen, Thomas / Olsen, Lisbeth Høier / Kilpeläinen, Tuomas O

Epigenetics

2023 Volume 18, Issue 1, Page(s) 2199374

Abstract: Profiling of circulating cell-free DNA (cfDNA) by tissue-specific base modifications, such as 5-methylcytosines (5mC), may enable the monitoring of ongoing pathophysiological processes. Nanopore sequencing allows genome-wide 5mC detection in cfDNA ... ...

Abstract	Profiling of circulating cell-free DNA (cfDNA) by tissue-specific base modifications, such as 5-methylcytosines (5mC), may enable the monitoring of ongoing pathophysiological processes. Nanopore sequencing allows genome-wide 5mC detection in cfDNA without bisulphite conversion. The aims of this study were: i) to find differentially methylated regions (DMRs) of cfDNA associated with obesity in Göttingen minipigs using Nanopore sequencing, ii) to validate a subset of the DMRs using methylation-specific PCR (MSP-PCR), and iii) to compare the cfDNA DMRs with those from whole blood genomic DNA (gDNA). Serum cfDNA and gDNA were obtained from 10 lean and 7 obese Göttingen Minipigs both with experimentally induced myocardial infarction and sequenced using Oxford Nanopore MinION. A total of 1,236 cfDNA DMRs (FDR<0.01) were associated with obesity. In silico analysis showed enrichment of the adipocytokine signalling, glucagon signalling, and cellular glucose homoeostasis pathways. A strong cfDNA DMR was discovered in
MeSH term(s)	Humans ; Swine ; Animals ; DNA Methylation ; Swine, Miniature/genetics ; Diabetes Mellitus, Type 2/genetics ; Nanopore Sequencing ; DNA ; Cell-Free Nucleic Acids/genetics ; Obesity/genetics ; RNA-Binding Proteins/genetics
Chemical Substances	DNA (9007-49-2) ; Cell-Free Nucleic Acids ; PPARGC1B protein, human ; RNA-Binding Proteins
Language	English
Publishing date	2023-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1559-2308
ISSN (online)	1559-2308
DOI	10.1080/15592294.2023.2199374
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A porcine model of subcutaneous Staphylococcus aureus infection: a pilot study.

Nielsen, Ole Lerberg / Mellergaard, Maiken / Frees, Dorte / Larsen, Maria Nygaard / Skov, Søren / Olsen, Lisbeth Høier / Reimann, Maria Josefine

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

2021 Volume 130, Issue 7, Page(s) 359–370

Abstract: In this descriptive pilot study, we aim to establish a porcine Staphylococcus aureus skin infection model by subcutaneous injection (s.c.) of the porcine S54F9 S. aureus strain in the groin area. Six pigs were used in the study: Five pigs were injected ... ...

Abstract	In this descriptive pilot study, we aim to establish a porcine Staphylococcus aureus skin infection model by subcutaneous injection (s.c.) of the porcine S54F9 S. aureus strain in the groin area. Six pigs were used in the study: Five pigs were injected with S. aureus, inocula ranging from 7 × 10
MeSH term(s)	Animals ; Disease Models, Animal ; Pilot Projects ; Sepsis/pathology ; Staphylococcal Infections/microbiology ; Staphylococcus aureus ; Swine
Language	English
Publishing date	2021-03-01
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	93340-5
ISSN	1600-0463 ; 0903-4641
ISSN (online)	1600-0463
ISSN	0903-4641
DOI	10.1111/apm.13101
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Article ; Online: Hyperglycemia-induced transcriptional regulation of ROCK1 and TGM2 expression is involved in small artery remodeling in obese diabetic Göttingen Minipigs.

Ludvigsen, Trine Pagh / Olsen, Lisbeth Høier / Pedersen, Henrik Duelund / Christoffersen, Berit Østergaard / Jensen, Lars Jørn

Clinical science (London, England : 1979)

2019 Volume 133, Issue 24, Page(s) 2499–2516

Abstract: Obesity and diabetes in humans are associated with hypertrophic remodeling and increased media:lumen ratio of small resistance arteries, which is an independent predictor of cardiovascular events. In order to minimize increases in media:lumen ratio, ... ...

Abstract	Obesity and diabetes in humans are associated with hypertrophic remodeling and increased media:lumen ratio of small resistance arteries, which is an independent predictor of cardiovascular events. In order to minimize increases in media:lumen ratio, hypertrophic remodeling should be accompanied by outward remodeling. We aimed to investigate the mechanisms of structural remodeling in small pial arteries (PAs) and terminal mesenteric arteries (TMAs) from obese Göttingen Minipigs with or without diabetes. Göttingen Minipigs received either control diet (lean control (LC)), high fat/high fructose/high cholesterol diet (FFC), or FFC diet with streptozotocin (STZ)-induced diabetes (FFC/STZ) for 13 months. At the end of the study (20 months), we assessed body weight, fasting plasma biochemistry, passive vessel dimensions, mRNA expression (matrix metallopeptidases 2/9 (MMP2, MMP9), tissue inhibitor of metallopeptidase 1 (TIMP1), transglutaminase 2 (TGM2), Rho-kinase 1 (ROCK1), TGFβ-receptor 2 (TGFBR2), and IGF1-receptor (IGFR1) genes), and immunofluorescence in PAs and TMAs. We performed multiple linear correlation analyses using plasma values, structural data, and gene expression data. We detected outward hypertrophic remodeling in TMAs and hypertrophic remodeling in PAs from FFC/STZ animals. ROCK1 and TGM2 genes were up-regulated in PAs and TMAs from the FFC/STZ group. Passive lumen diameter (PLD) of TMAs was correlated with plasma values of glucose (GLU), fructosamine (FRA), total cholesterol (TC), and triglycerides (TGs). ROCK1 and TGM2 expressions in TMAs were correlated with PLD, plasma GLU, fructosamine, and TC. ROCK1 and TGM2 proteins were immunolocalized in the media of PAs and TMAs, and their fluorescence levels were increased in the FFC/STZ group. Hyperglycemia/hyperlipidemia is involved in regulation of ROCK1 and TGM2 expression leading to outward remodeling of small resistance arteries in obese diabetic Göttingen Minipigs.
MeSH term(s)	Animals ; Arteries ; Cholesterol, Dietary/adverse effects ; Diabetes Mellitus, Experimental ; Diet/adverse effects ; Diet, High-Fat/adverse effects ; Fructose/adverse effects ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Hyperglycemia/physiopathology ; Male ; Mesenteric Arteries ; Obesity ; Pia Mater/blood supply ; Swine ; Swine, Miniature ; Transglutaminases/genetics ; Transglutaminases/metabolism ; Vascular Remodeling ; rho-Associated Kinases/genetics ; rho-Associated Kinases/metabolism
Chemical Substances	Cholesterol, Dietary ; Fructose (30237-26-4) ; transglutaminase 2 (EC 2.3.2.-) ; Transglutaminases (EC 2.3.2.13) ; rho-Associated Kinases (EC 2.7.11.1) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2019-12-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20191066
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Article ; Online: Functional and morphological renal changes in a Göttingen Minipig model of obesity-related and diabetic nephropathy.

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

Scientific reports

2023 Volume 13, Issue 1, Page(s) 6017

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Swine ; Male ; Humans ; Diabetic Nephropathies/pathology ; Swine, Miniature ; Kidney/pathology ; Obesity/pathology ; Glomerular Basement Membrane/pathology ; Diabetes Mellitus/pathology
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-32674-6
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

Order via subito

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In stock of ZB MED Cologne/Königswinter

Order via subito

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Order via subito

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Order via subito

Inter-library loan at ZB MED

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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito