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Growth (kg; mean ± SEM, n = 6 pigs per group) over time for Yucatan miniature swine on standard grower pig diet (Std) compared with those fed a diet high in salt, fat, and sugar (HSFS). Differences (*, P < 0.05; ‡, P < 0.001) between dietary treatments were assessed by 2-way repeated-measures ANOVA with Bonferroni posthoc tests.
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Radiotelemetry was used to evaluate diet-related elevation of blood pressure in adult Yucatan miniature swine. Systolic arterial blood pressure (SAP), diastolic atrial blood pressure (DAP), heart rate, and locomotor activity were assessed in 9- or 11-mo-old Yucatan miniature pigs fed a standard diet or a North American-type diet high in salt, fat,...
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Context 1
... performance. Both groups (n = 6; 3 male, 3 female) of Yucatan minipigs were similar in mean birth weight (standard diet group, 1.00 ± 0.07 kg; HSFS diet group, 1.01 ± 0.05 kg; P = 0.830) and weaning weight (standard, 6.04 ± 0.49 kg; HSFS, 5.82 ± 0.30 kg; P = 0.714). However, the pigs on the HSFS diet grew at a slower rate than did the control pigs ( Figure 2); that is, be- cause of the higher energy density and higher energy-to-protein ratio of the diet, HSFS-fed pigs consumed less protein and grew slower (Figure 2), particularly between 1 to 4 mo of age, than did standard-fed pigs. Average relative feed intake was lower in HSFS pigs between 1 and 4 mo old (standard, 46.6 ± 1.2 g/kg body weight/d; HSFS, 42.5 ± 1.1 g/kg body weight/d; P < 0.05) but not between 4 and 7 mo old (standard, 27.4 ± 0.9 g/kg body weight/d; HSFS, 27.0 ± 0.4 g/kg body weight/d) or from 7 mo to necropsy (standard, 21.6 ± 0.6 g/kg body weight/d; HSFS: 21.6 ± 0.7 g/kg body weight/d). Therefore, the HSFS group was main- tained on the diet 2 mo longer before hemodynamic recordings, and body weights at surgery (standard: 69.15 ± 2.62 kg, 9 mo old; HSFS: 69.67 ± 5.39 kg, 11 mo old; P = 0.932) and at necropsy (stan- dard: 72.20 ± 2.62 kg, 10 mo old; HSFS: 72.72 ± 4.44 kg, 12 mo old; P = 0.922) were similar between groups. Moreover, at the end of the study, relative backfat thickness (dorsal midline, caudal to the last rib), a measure of subcutaneous fat deposition, was similar between groups (standard, 0.85 ± 0.08 mm backfat per kilogram body weight; HSFS, 0.86 ± 0.06 mm backfat per kilogram body weight; P = 0.811). Therefore, body weight was not a confound- ing factor in this study, thereby supporting direct comparison of dietary factors between the standard and HSFS ...
Context 2
... performance. Both groups (n = 6; 3 male, 3 female) of Yucatan minipigs were similar in mean birth weight (standard diet group, 1.00 ± 0.07 kg; HSFS diet group, 1.01 ± 0.05 kg; P = 0.830) and weaning weight (standard, 6.04 ± 0.49 kg; HSFS, 5.82 ± 0.30 kg; P = 0.714). However, the pigs on the HSFS diet grew at a slower rate than did the control pigs ( Figure 2); that is, be- cause of the higher energy density and higher energy-to-protein ratio of the diet, HSFS-fed pigs consumed less protein and grew slower (Figure 2), particularly between 1 to 4 mo of age, than did standard-fed pigs. Average relative feed intake was lower in HSFS pigs between 1 and 4 mo old (standard, 46.6 ± 1.2 g/kg body weight/d; HSFS, 42.5 ± 1.1 g/kg body weight/d; P < 0.05) but not between 4 and 7 mo old (standard, 27.4 ± 0.9 g/kg body weight/d; HSFS, 27.0 ± 0.4 g/kg body weight/d) or from 7 mo to necropsy (standard, 21.6 ± 0.6 g/kg body weight/d; HSFS: 21.6 ± 0.7 g/kg body weight/d). Therefore, the HSFS group was main- tained on the diet 2 mo longer before hemodynamic recordings, and body weights at surgery (standard: 69.15 ± 2.62 kg, 9 mo old; HSFS: 69.67 ± 5.39 kg, 11 mo old; P = 0.932) and at necropsy (stan- dard: 72.20 ± 2.62 kg, 10 mo old; HSFS: 72.72 ± 4.44 kg, 12 mo old; P = 0.922) were similar between groups. Moreover, at the end of the study, relative backfat thickness (dorsal midline, caudal to the last rib), a measure of subcutaneous fat deposition, was similar between groups (standard, 0.85 ± 0.08 mm backfat per kilogram body weight; HSFS, 0.86 ± 0.06 mm backfat per kilogram body weight; P = 0.811). Therefore, body weight was not a confound- ing factor in this study, thereby supporting direct comparison of dietary factors between the standard and HSFS ...
Citations
... In humans, hypertension is often present in obese and diabetic individuals 25 and is partly related to the dietary salt intake 26,27 . In the present study, feeding an FFC diet with or without concomitant presence of diabetes and with or without additional dietary salt did not lead to increased BP, which is in contrast to what has previously been observed in pigs fed a high fat, high sugar and/or salt-containing diet, indicating that the salt content and/or feeding period used here may have been insufficient to induce chronic hypertension 28,29 . However, in the current study, the presence of diabetes led to increased HR independent of the salt content of the diet and independent of increases in BP. ...
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.
... Pigs fed a diet rich in fat, sucrose and salt have increased blood pressure. 15 Similar reports in human studies indicate that salt prevents the development of obesity in men. 16,17 Overall, it is extremely important to investigate sex-specific aspects of cardiovascular remodelling in rodent models of diet-induced CVD, since it has not been thus far explored for combinations of sugar, fat and salt overload. ...
Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style‐induced cardiovascular disease has not thus far been explored in these models. Thus, this study investigated cardiovascular remodelling in C57BL/6J mice fed a diet rich in saturated fat, sucrose and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodelling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance as assessed by serum glucose, insulin and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in either male or female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta showed media thickening in male mice, but in the female it was only observed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Therefore changes in LV dimensions and arterial remodelling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodelling after 12 weeks of HFSS feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy and intramyocardial artery remodelling.
... Blood glucose remained unchanged and in agreement to similar fasting levels seen in other minipig studies. 11,39 A glucose or insulin challenge might have provided; however, more information about the effects of ad libitum feeding. ...
Miniature pig models for human metabolic disorders such as obesity and Metabolic Syndrome are gaining popularity. However, in-depth knowledge on the phenotypic and metabolic effects of metabolic dysregulation is lacking and ad libitum feeding is not well characterized in these pig breeds. Therefore, an investigation was performed into the metabolome of Yucatan minipigs fed ad libitum or restrictive. Furthermore, we used cloned and conventional minipigs to assess if cloning reflects a presumably lowered variation between subjects. For five months, 17 female Yucatan minipigs were fed either ad libitum or restrictive a western style diet. Serum, urine and liver tissues were collected and analyzed by non-targeted liquid chromatography−mass spectrometry metabolomics and by biochemical analyses. Several metabolic pathways were deregulated as a result of obesity and increased energy dense feed intake, particularly the hepatic glutathione pathway and the pantothenic acid and tryptophan metabolic pathways in serum and urine. Although cloned minipigs were phenotypically similar to wild-type, metabolomics analysis of serum and liver tissues showed several altered pathways, such as amino acid and purine metabolism. These changes, as an effect of cloning, could limit the use of cloned models in dietary intervention studies and provides no evidence of decreased variability between subjects.
... However, the combination of fat, sugar, and salt overload is less exploited in literature, and the sex response to these nutrients combined. Pigs fed a diet rich in fat, sucrose, and salt have increased blood pressure (Myrie et al., 2012). Similar reports in human studies indicate that salt prevents the development of obesity in men (Polonia e Martins, 2009;Ekinci et al., 2011). ...
Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease was not exploited so far. Thus, this study investigated cardiovascular remodeling in C57BL/6J mice fed a diet rich in saturated fat, sucrose, and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose, and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodeling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance assessed by serum glucose, insulin, and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in male and female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta had intima-media thickening in male mice, but in the female, it was only noticed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Changes in LV dimensions and the arterial remodeling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodeling after 12 weeks of high-fat, high-sucrose, high-salt feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy, and intramyocardial artery remodeling.
... Recently, the use of actigraph to measure LA has been applied to other large mammals such as pigs (20). In general, LA for minipigs has been measured by a probe placed in the body using a telemetric system (13,26). The LA measurements made here using an actigraph were largely consistent with the results obtained using the telemetric system. ...
... The LA measurements made here using an actigraph were largely consistent with the results obtained using the telemetric system. However, in the present study, the LA during the nocturnal period was higher than those previously reported (13,26). This difference may be because of the different levels in sensitivity in recording LA. ...
The effects of dietary and lighting conditions on diurnal rhythm of locomotor activity (LA) and body temperature (BT) using four adult male microminipigs were investigated. Different feeding times, diet and lighting conditions were applied sequentially for 3 weeks in each phase as follows: Phase I: Morning mealtime, normal diet, 12-h lights on; phase II: mealtime changed to afternoon; phase III: diet changed to high-fat diet; phase IV: lighting changed to 20-h on; and phase V: phase I repeated. LA was measured by an actigraph which was worn on the body of each pig. A BT recording module (Thermochron Type-SL) was implanted in the neck subcutaneously. Phase II increased BT compared with phase I. Phase III increased LA and BT compared with phase II. Phase IV increased LA compared with phase III. LA in phase V was higher compared with phase I. These results can be extrapolated to other diurnal animals such as humans. This study provides an example of the effects of diet and lighting on biological activities in microminipigs under low-invasive procedures measuring LA and BT, leading to low variations in these measures.
... To avoid confounders (e.g., anesthesia, stress, etc.) data are included only from experiments where mean arterial pressure (MAP) has been measured telemetrically in chronically instrumented, conscious, and nonstressed animals. Species included are: dog (Haushalter et al. 2008), rat (Sithisarn et al. 2013), rabbit (Guild et al. 2012), guinea pig (Hess et al. 2007), mouse (Kim et al. 2008), cynomolgus monkey (Haushalter et al. 2008), sheep (King et al. 2007), Yucatan miniature swine (Myrie et al. 2012), G€ ottingen minipig (Stubhan et al. 2008), Rhesus monkey (Regan et al. 2009), marmoset (Wood et al. 2005), horse (body mass estimated) (Hornicke et al. 1977), three-toed sloth (Duarte et al. 2003) and human (Damkjaer et al. 2014). Human data are not telemetric. ...
Mean arterial pressure (MAP) is surprisingly similar across different species of mammals, and it is, in general, not known which factors determine the arterial pressure level. Mammals often have a pronounced capacity for sustained physical performance. This capacity depends on the vasculature having a flow reserve that comes into play as tissue metabolism increases. We hypothesize that microvascular properties allowing for a large vascular flow reserve is linked to the level of the arterial pressure.To study the interaction between network properties and network inlet pressure, we developed a generic and parsimonious computational model of a bifurcating microvascular network where diameter and growth of each vessel evolves in response to changes in biomechanical stresses. During a simulation, the network develops well-defined arterial and venous vessel characteristics. A change in endothelial function producing a high precapillary resistance and thus a high vascular flow reserve is associated with an increase in network inlet pressure. Assuming that network properties are independent of body mass, and that inlet pressure of the microvascular network is a proxy for arterial pressure, the study provides a conceptual explanation of why high performing animals tend to have a high MAP.
... To avoid confounders (e.g., anaesthesia, stress etc.) we have chosen only to include data from experiments where MAP have been measured telemetrically in chronically instrumented, conscious and non-stressed animals. Species included are: rat (Sithisarn et al. 2013), rabbit (Malpas et al. 1997), guinea pig (Provan et al. 2005), mouse (Kim et al. 2008), cynomolgus monkey (Haushalter et al. 2008), sheep (King et al. 2007), dog (Mckee et al. 2014) Yucatan miniature swine (Myrie et al. 2012), G€ ottingen minipig (Markert et al. 2009), Rhesus monkey (Regan et al. 2009), tree toed sloth (Duarte et al. 2003), marmoset (Horii et al. 2002), horse (Hornicke et al. 1977) and humans (Head et al. 2014). Please note that for humans there are no telemetric data, values are from an epidemiological survey. ...
Giraffes are the tallest living animals and endowed with the highest arterial blood pressure of any animal on Earth. Here we present novel data on kidney function in this extraordinary animal obtained over the course of two major expeditions in 2010 and 2012. As expected, the anaesthetised giraffes had very high mean arterial blood pressure ranging between 150 and 300 mmHg. However, despite the high filtration pressure, the rate of glomerular filtration (GFR) was only 0.7 ± 0.2 ml/min/kg, which is approximately 40 % below similar-sized mammals. The renal blood flow of 3.1 l/min accounts for approximately 20 % of cardiac output, and the calculated filtration fraction (GFR/ERPF) was approximately 0.3, and hence within typical mammalian values. The normal kidney function of the giraffes appears due to very high interstitial pressures within the kidney, a feature that is possible due to the very thick and strong capsule surrounding the kidney in combination with a vascular valve at the entrance of the renal vein into the abdominal cava. These relatively simple structural modifications normalize the Starling forces driving filtration over the Bowman capsula.
... There have been a number of studies that have examined the effect of a high salt diet administered postnatally, as a secondary lifestyle insult, on blood pressure in IUGR offspring [95,117,[201][202][203]. Interestingly, several studies have shown that the increase in blood pressure in response to a high salt diet is similar between IUGR offspring and non-IUGR offspring [117,204], whereas some report salt-sensitive hypertension [93] and others report a reduction in blood pressure [95]. ...
Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of "programming". The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.
... The implication seems to be that arterial pressure To avoid confounders (e.g., anaesthesia, stress etc.) we have chosen only to include data from experiments where MAP have been measured telemetrically in chronically instrumented, conscious and non-stressed animals. Species included are: rat (Sithisarn et al. 2013), rabbit (Malpas et al. 1997), guinea pig (Provan et al. 2005), mouse (Kim et al. 2008), cynomolgus monkey (Haushalter et al. 2008), sheep (King et al. 2007), dog (Mckee et al. 2014) Yucatan miniature swine (Myrie et al. 2012), G€ ottingen minipig (Markert et al. 2009), Rhesus monkey (Regan et al. 2009), tree toed sloth (Duarte et al. 2003), marmoset (Horii et al. 2002), horse (Hornicke et al. 1977) and humans (Head et al. 2014). Please note that for humans there are no telemetric data, values are from an epidemiological survey. ...
Background: The tallest animal on earth, the giraffe (Giraffa camelopar-dalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal hae-modynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. Methods: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and his-tological characteristics of vascular and renal tissues were determined. Results: GFR averaged 342 AE 99 mL min À1 and ERPF 1252 AE 305 mL min À1. RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 AE 2 mmHg and renal venous pressure 32 AE 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 AE 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 AE 0.5 mIU L À1 and 9.1 AE 1.5 pg mL À1 respectively. Conclusion: In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP.
... Previous studies have reported that the hemodynamic parameters of minipigs were characterized by a highly stable state with very low variability, resulting in a highly sensitive model for detecting possible drug-induced effects and leading to an optimization of the statistical power of an experimental model and the possibility to reduce the number of animal used (Bode et al., 2010;Stubhan et al., 2008). Diurnal rhythm of HR in minipigs has been reported in previous studies, which found that HR during light period was higher than in the dark periods when the animals were housed individually, but animals housed in pairs have no diurnal variation (Kuwahara et al., 2004;Myrie et al., 2012). Another study reported a significant increase in HR at night when minipigs were fed shortly before the start of dark period (Stubhan et al., 2008). ...
