HF Animals Research Articles

Intimal Hyperplasia in Mouse Vein Grafts Is Regulated by Flow

Altered flow conditions are presumed to cause stenosis in vein grafts due to exaggerated neointimal formation. The aim of this study was to establish a mouse model of flow-regulated intimal hyperplasia (IH) in vein grafts. The caval vein was grafted into the common carotid artery of 38 mice, followed by modulation of the blood flow, resulting in vein grafts with high (HF) and low flow (LF). The vessel wall thickening was evaluated after 3, 14 and 42 days by morphometric analyses and immunohistochemistry. There was an immediate significant change in flow, which was persistent throughout the time of observation. After 42 days, flow was increased 2.7 times in HF animals compared to LF animals. The vessel wall was composed of two layers where the inner layer was positive for α-actin and considered as IH. The area of neointimal formation was 74% larger in the LF group compared to the HF group. The present study demonstrates that flow regulates IH in vein grafts in mice. This model gives the potential to study the effect of shear stress on vascular biology in genetically modified animals.

The Plasma Level of Insulin-like Growth Factor-I (IGF-I) in Relation to Mammary Circulation and Milk Yield in Two Different Types of Crossbred Holstein Cattle

The objective of the present study was to determine the plasma level of insulin-like growth factor-I (IGF-I) in relation to mammary blood flow and milk yield including biological variables of relevance to milk synthesis in two different types of crossbred Holstein cattle at 3 different stages of lactation. Eight heifers were 87.5% HF and eight 50% HF animals were selected for the experiments. The three stages of lactation tested were: early lactation (30 days postpartum), mid-lactation (120 days postpartum) and late lactation (210 days postpartum). Animals in each group were fed a concentrate and rice straw treated with 5% urea as the source of roughage throughout the experiments. In early lactation, mammary blood flow and milk yield of 87.5% HF animals were significantly higher than those of 50% HF animals. In mid- and late lactation, both mammary blood flow and milk yield showed a proportional decrease from the early lactating period of 87.5% HF animals. The trends for persistency were observed in 50% HF animals as for udder blood flow and milk yield throughout the experimental periods. The plasma glucose level of the 50% HF animals was significantly higher than those of 87.5% HF animals in both early and mid-lactation. The concentrations of arterial plasma free fatty acids (C16 to C18) were higher in 50% HF animals as compared with 87.5% HF animals in all periods of study. In early lactation, the concentration of plasma growth hormone (GH) of 87.5% HF animals was higher than those of the 50% HF animals, thereafter the mean level of plasma growth hormone declined in both mid- and late lactation. The concentration of plasma IGF-I of 50% HF animals was significantly higher than those of 87.5% HF animals in all stages of lactation. There were no differences among stages of lactation for the levels of plasma IGF-I, insulin and growth hormone in 50% HF animals. In 87.5% HF animals, the plasma levels of both IGF-I and insulin were lower in early lactating period while it showed an increase during mid- and late lactation. The present results indicated that the regulatory role for the higher mammary blood flow and milk yield during lactation in 87.5% HF are not mediated via the higher level of circulating IGF-I. Differences in mammary blood flow and milk yield between 50% HF and 87.5% HF animals are in part due to a higher concentration of circulating growth hormone. The lower level of circulating growth hormone in 50% HF animals would be regulated by higher levels of IGF-I, free fatty acid and glucose in plasma. (Asian-Aust. J. Anim. Sci. 2004. Vol 17, No. 3 : 343-348)

Studies on the Mode of Uptake of Plasma Glucose, Acetate, β-hydroxybutyrate Triglyceride Fatty Acids and Glycerol by the Mammary Gland of Crossbred Holstein Cattle Feeding on Different Types of Roughage

The present experiment was carried out to study the utilization of substrates in the mammary gland of crossbred Holstein Friesian during feeding on different types of roughage. Sixteen pregnant crossbred Holstein heifers consisted of two breed types of eight animals each; Holstein Friesian×Red Sindhi (50:50=50%HF) and Holstein Friesian×Red Sindhi (87.5:12.5=87.5%HF). Animals were divided into four groups of the same breed type in each group which were fed with either rice straw treated with 5% urea or pangola hay (Digitaria decumbens) as the source of roughage throughout the experiments. Four consecutive experimental periods were carried out in late pregnancy (20-23 days before parturition), early lactation (30 days postpartum), mid-lactation (120 days postpartum) and late lactation (210 days postpartum). Measurement of mammary blood flow in combining with measurement of AV difference was performed for the mammary uptake of substrates. In the period of lactation, udder blood flow was nearly three times higher than that of late pregnant period (p<0.05) in both 50%HF and 87.5%HF feeding on either hay or urea treated rice straw. During mid- and late lactation of both groups of 87.5%HF animals, mammary blood flow and milk yield showed decrease when compared to those during the early lactating period while the trends for persistency were apparent in both groups of 50%HF animals throughout experimental periods. The mean arterial plasma concentrations of glucose, acetate, β-hydroxybutyrate and free glycerol in each group remained constant throughout experimental periods. During late pregnancy in all groups, the AV difference and extraction ratio of glucose, β-hydroxybutyrate and triacylglycerol across the mammary gland markedly lowered (p<0.05), which coincided with a lower net uptake by the mammary gland in comparison to the early lactating period. The mean arterial plasma concentration, AV difference and extraction ratio for acetate showed no significant differences between late pregnancy and the early lactating period. The AV difference of free glycerol showed apparent release from mammary tissue during late pregnancy in all groups. In mid- and late lactation, the mammary uptake for glucose, acetate and β-hydroxybutyrate in both groups of 87.5%HF animals showed apparent decrease as compared to that in the early lactating period, whereas no appearances were observed in 50%HF animals feeding either hay or urea treated rice straw. The mean arterial plasma concentrations for free fatty acid (FFA) and triacylglycerol (C16 to C18) were higher in late pregnancy than in early lactation in both types of crossbred animals. The values of AV difference and the net uptake by the mammary gland for FFA were variable during late pregnancy and lactating periods in all groups. There were no significant differences for AV difference, extraction ratio and net uptake of triacylglycerol during lactation advance in both groups of 50%HF and 87.5%HF animals feeding either hay or urea treated rice straw. These results suggest that the adaptations to either hay or urea treated rice straw by the mammary gland of crossbred HF animals allow for an adequate nutrient supply during pregnancy and lactation. There is no difference in the mode of mammary uptake of substrates in the same crossbred animals in response to feeding hay or urea treated rice straw. The differences in utilizing nutrients by the mammary gland for milk production between 87.5%HF and 50%HF animals would be dependent on changes in both intra-mammary factors and extra-mammary factors. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 10 : 1445-1452)

Reversal of Diet-induced Glucose Intolerance by Hepatic Expression of a Variant Glycogen-targeting Subunit of Protein Phosphatase-1

Glycogen-targeting subunits of protein phosphatase-1 facilitate interaction of the phosphatase with enzymes of glycogen metabolism. Expression of one family member, PTG, in the liver of normal rats improves glucose tolerance without affecting other plasma variables but leaves animals unable to reduce hepatic glycogen stores in response to fasting. In the current study, we have tested whether expression of other targeting subunit isoforms, such as the liver isoform G(L), the muscle isoform G(M)/R(Gl), or a truncated version of G(M)/R(Gl) termed G(M)DeltaC in liver ameliorates glucose intolerance in rats fed on a high fat diet (HF). HF animals overexpressing G(M)DeltaC, but not G(L) or G(M)/R(Gl), exhibited a decline in blood glucose of 35-44 mg/dl relative to control HF animals during an oral glucose tolerance test (OGTT) such that levels were indistinguishable from those of normal rats fed on standard chow at all but one time point. Hepatic glycogen levels were 2.1-2.4-fold greater in G(L)- and G(M)DeltaC-overexpressing HF rats compared with control HF animals following OGTT. In a second set of studies on fed and 20-h fasted HF animals, G(M)DeltaC-overexpressing rats lowered their liver glycogen levels by 57% (from 402 +/- 54 to 173 +/- 27 microg of glycogen/mg of protein) in the fasted versus fed states compared with only 44% in G(L)-overexpressing animals (from 740 +/- 35 to 413 +/- 141 microg of glycogen/mg of protein). Since the OGTT studies were performed on 20-h fasted rats, this meant that G(M)DeltaC-overexpressing rats synthesized much more glycogen than G(L)-overexpressing HF rats during the OGTT (419 versus 117 microg of glycogen/mg of protein, respectively), helping to explain why G(M)DeltaC preferentially enhanced glucose clearance. We conclude that G(M)DeltaC has a unique combination of glycogenic potency and responsiveness to glycogenolytic signals that allows it to be used to lower blood glucose levels in diabetes.

Effect of high-fat diet on body composition and hormone responses to glucose tolerance tests.

To determine potential hormonal mediators of the effect of high-fat diets on the development of insulin resistance, blood leptin, growth hormone (GH), glucose, and insulin responses to a 2 g/kg BW oral glucose challenge were evaluated in weanling female Sprague Dawley rats that were randomly assigned to a high-fat (HF, 39% of calories, 20% fat by weight; n = 10) and moderate-fat (MF, 22% of calories, 10% fat by weight; n = 10) diets. Oral glucose challenges were administered following 5, 7, and 9 wk on the feeding trial. Animals were provided diet in excess of their requirements for growth. Body mass analysis was conducted by dual X-ray absorptiometry (DXA) on the 6th, 8th, and 10th weeks of the trial. HF animals gained more weight after 7 wk, had greater body fat than the MF animals, and similar glucose responses to the oral glucose challenges. HF rats secreted more insulin and leptin compared to MF animals. Lean body mass and serum GH and IGF-I concentrations were not different between the groups. Results of this study demonstrate that leptin but not GH or IGF-I is involved in the development of insulin resistance in growing rats as a result of excess energy intake in the form of dietary fat.

Glucose metabolism in crossbred Holstein cattle feeding on two types of roughage at different stages of lactation

An experiment was performed to study the glucose kinetics of crossbred Holstein cattle feeding on either hay or 5% urea-treated rice straw during early lactation (30 days post partum), mid-lactation (120 days post partum) and late lactation (210 days post partum). Two breeds: Holstein Friesian×Red Sindhi (50:50=50% HF) and Holstein Friesian×Red Sindhi (87.5:12.5=87.5% HF) were used. In early lactating 87.5% HF animals feeding on either hay or urea-treated rice straw, the high milk yields and lactose secretion were related to glucose uptake by the udder and udder blood flow as compared with those of 50% HF animals. Marked decreases in udder blood flow, glucose uptake, lactose secretion and milk yield were apparent in mid- and late lactation of both groups of 87.5% HF animals. In contrast, both groups of 50% HF animals showed no significant changes in udder blood flow, udder glucose uptake, lactose secretion and milk yields throughout the course of lactation. Total glucose entry rate using 3-[ 3H] glucose infusion, recycling of glucose carbon and plasma glucose clearance significantly increased during late lactation for 50 and 87.5% HF animals feeding on urea-treated rice straw. The utilization rates of glucose using [U- 14C] glucose infusion were not significantly different among groups of animals and periods of lactation. It can be concluded that 87.5% HF animals have the genetic potential for a higher milk yield, but a shorter peak yield and poorer persistence in comparison with 50% HF animals. Changes in the utilization of glucose by the mammary gland for milk production in both groups of crossbred animals during feeding on either hay or urea-treated rice straw would be dependent on intramammary changes.

Glucose metabolism in vivo in crossbred Holstein cattle feeding on different types of roughage during late pregnancy and early lactation

An experiment was carried out to study the glucose kinetics of crossbred Holstein cattle feeding on either hay or 5% urea treated rice straw during late pregnancy (21 days prepartum) and early lactation (30 days postpartum). In all 16 pregnant heifers (23–25 months of age) were selected for the experiments, including eight animals of two breed types, Holstein Friesian×Red Sindhi (50:50=50% HF) and Holstein Friesian×Red Sindhi (87.5:12.5=87.5% HF). They were divided into four groups of four animals each. Animals from the same breed type in each group were fed with either rice straw treated with 5% urea or pangola hay ( Digitaria decumbens) as the source of roughage throughout the experiments. The glucose turnover rate in both types of crossbred Holstein cattle was determined using a continuous infusion of [U- 14C] and 3-[ 3H]glucose during late pregnancy and early lactation. Total glucose entry and utilization rates increased significantly during lactation for all groups. Recycling of [C]glucose was, approximately, 20% in both crossbred cattle fed either hay or urea treated rice straw and was unaffected by the stage of late pregnancy or early lactation. Comparing 50 and 87.5% HF animals, arterial plasma glucose concentrations were slightly higher during pregnant periods but significantly higher in lactating periods in 50% HF animals. The ratio of specific radioactivity of arterial blood bicarbonate relative to that of arterial blood [ 14C]glucose in the lactating period, significantly decreased in 50% HF animals fed either urea treated rice straw or hay. An increase in udder blood flow during early lactation was significantly higher in 87.5% HF animals than in 50% HF animals. The uptake, arteriovenous differences and extraction ratio for glucose across the udder, significantly increased in the lactating period for all crossbred animals. Glucose uptake by the udder of 87.5% HF animals accounted for 65% of the total glucose turnover rate compared to a value of 46% in the lactating 50% HF animals. It can be concluded that both crossbred cattle fed either urea treated rice straw or hay exhibit the same body glucose turnover rate. The 87.5% HF animal has the genetic potential for a high milk yield and has high body and udder glucose metabolisms compared with 50% HF animals.

Poloxamer 407-induced atherogenesis in the C57BL/6 mouse

Poloxamer 407 (P-407) induces hyperlipidemia in the rat. It was the purpose of this investigation to determine if chronic P-407 administration would produce atherogenic arterial lesions in the C57BL/6 mouse, a strain reported to be susceptible to hyperlipidemia-induced atherosclerotic plaque formation. One injection (i.p.) of P-407 (0.5g/kg) produced hypercholesterolemia in the mouse that peaked at 24 h and returned to control levels by 96 h following treatment. Four groups of mice were maintained: (1) saline injected (C); (2) P-407-injected (0.5g/kg every 3rd day) (P); (3) P-407 injected plus cholic acid in the diet (PC); and (4) mice fed a high cholesterol (CHOL) diet containing cholic acid (HF). Mice from each group were sacrificed following 90, 145, 200, or 300 days of treatment. Plasma lipid concentrations, hepatic CHOL concentrations (145 and 300 day), and aortic atherogenic lesion areas were measured. Plasma CHOL and triglyceride remained at control levels throughout the 300 days in the C group. CHOL of the HF animals plateaued at approximately 225 mg/dl. P-407 produced CHOL concentrations of 600 mg/dl in P mice and 1000–1500 mg/dl in PC animals. There was no lesion formation in C mice. However, by 90 days lesions were present in the three other groups. Size of the lesions progressed through day 300 with the largest lesions (184.33+27.99 μ 2×10 −3) being present in the PC mice. HF and P animals had lesions of 70.50+11.35 and 43.33+7.88 μ 2×10 −3, respectively. This study provides an animal model where atherogenesis has been produced with hyperlipidemia induced using a chemical agent.

25—CROSS-BREEDING STUDIES WITH SELECTED FLEECE LINES OF SCOTTISH BLACKFACE SHEEP

This paper presents the results of an investigation of the fleeces of sheep that were the offspring of crosses (HF) between a hairy line (HH) of the Scottish Blackface breed that had been selected for 20 years for hairiness and a fine line (FF) that had been selected for fine fleeces. Other crosses investigated were between each of the selected lines and an unselected Control (CC) line (HC and FC), and with the Wensleydale breed (WH and WF). The lines had been selectively bred on an index of wool-fibre medullation determined from an eight-week-lamb coat sample, and there was some evidence of heterosis in the index of HC lambs, the values being closer to the value in hairy lambs than the mid-parent value. Fibre-type array (FTA) determined at the same age showed that HC and HF animals were more hairy than Controls, while FC lambs had finer arrays. The Wensleydale-cross lambs had considerably reduced hair coverage and lower hair densities than the Blackface, and FTAs showed a shift from the 100% Plateau arra...

Effect of Early Nutrition on Serum Cholesterol Levels in Adult Rats Challenged with High Fat Diet

Early exposure to cholesterol-enriched, high fat diets has been reported to affect serum cholesterol levels in adult rats. In this study, we investigated the role of dietary fat alone, without cholesterol, by feeding to pregnant rats (from day 18 of gestation) experimental diets containing either high fat (corn oil), low sucrose (HF) or low fat, high sucrose (HS). After birth, mothers and pups were fed the diets until weaning (30 days), when serum cholesterol levels were the same in both groups of pups. Animals were fed stock diet until 7 months. At that time, half the animals from each original group (HF or HS) were challenged with HF diet for 3 days; the other half were fed stock diet. There was no significant difference in serum cholesterol between HF and HS animals fed stock diet: HF, 73 ± 7 mg/dl (n = 11); HS, 80 ± 19 (6); P > 0.25. Animals originally fed HF diet significantly raised serum cholesterol in response to late HF challenge (140 ± 31 mg/dl, n = 10, P < 0.001 vs. stock fed); the original HS-fed group did not (93 ± 7 mg/dl, n = 5, P > 0.19). Early exposure to HF diet, even without cholesterol, could evoke a hypercholesterolemic response in adulthood following challenge by brief exposure to HF diet.

Influence of perinatal nutrition on hepatic drug metabolism in the adult rat.

Pregnant rats were fed high-fat (HF, 35% calories) or low-fat (LF, 5% calories) diet from 18 days of gestation to the end of the suckling period. Thereafter, male progeny were fed stock diet for 6 months, then sacrificed or challenged for 3 days with HF diet. There were no immediate posttreatment effects at 30 days of age on liver microsomal cytochrome P-450 or b5, aminopyrine (AP) N-demethylase or benzo(a)pyrene (BP) hydroxylase. At 7 months, cytochrome P-450 was lower in LF-fed than in HF-fed animals. High-fat challenge reduced cytochrome P-450 and cytochrome b5 content in both groups, AP N-demethylase only in LF animals and BP hydroxylase only in HF animals. These differential effects of perinatal exposure to diet on the later response of microsomal mixed-function oxidases to fat challenge suggest that early dietary experience may regulate the pattern of drug metabolism in adult life.

Influence de l’environnement sur les composantes du groupe social chez le Daim Cervus (Dama) dama L.

The patterns of social grouping of free ranging fallow deer, Cervus (Dama) dama, have been studied outside the breeding season for two consecutive years, in Alsace (N.E. France). Comparisons are made between animals living in a forest environment (HF animals) and others living in a more open habitat (HO animals), as well as with fallow deer inhabiting an intermediate, semi-closed environment (HI animals). Group characteristics are compared : occurence of the various grouping patterns (including solitary individuals), group size and composition, stability of social groups, and intra-group spacing. The composition of social groups varies greatly within a given population, depending upon the environmental conditions. All female groups are the most frequently observed in both forest and open habitats, whereas heterosexual groups rank a close second in open areas. Solitary animals are more frequently seen in forest environments than in open ones (Table I). The average overall group size is larger in open habitats (Table II). Group composition is also less stable, and group splitting more frequent, in open environments (Table III). Inter-individual distances between females are greater in forest habitats.

Effect of dietary histidine on olfaction, and rat brain and muscle concentration of histidine-containing dipeptides.

Abstract—Young adult male rats were fed three diets; one was devoid of histidine (HF), the second supplied the maintenance requirement (M, 3.7% protein, 0.07% histidine), and the third provided an optimal amount of histidine for growth (G, 10.0% protein, 0.21% histidine). The M diet was pair‐fed with the HF diet. After an 11 weeks experimental period, some HF animals were given the M diet for an 11 day repletion period. On the HF diet carnosine in the olfactory bulb and pectoral muscle, homocarnosine in whole brain and hemoglobin were sharply and significantly reduced in concentration below the levels found in the M and G groups. During the 11 day repletion period all concentrations except for hemoglobin returned to normal. Comparison of olfactory ability between M and HF rats showed no significant difference indicating that if carnosine is involved in olfaction, the amount required must be very small. Restricted food intake had no apparent effect on the concentration of histidine‐containing dipeptides but did influence hemoglobin concentration. The HF rats appeared to exhibit an altered state of emotionality compared to either of the other two treatment groups.

Increased Hepatic Gluconeogenesis without a Rise of Glucagon Secretion in Rats Fed a High Fat Diet

We have recently demonstrated that in rats fed a high protein, carbohydrate-free (HP) diet plasma glucagon and liver cyclic AMP are increased and as a result hepatic gluconeogenesis is stimulated. To determine whether increased protein intake or lack of dietary carbohydrate was responsible for these changes, the effects of a high fat, carbohydrate-free (HF) diet on plasma glucagon and insulin, liver cyclic AMP and hepatic gluconeogenesis were determined. Perfused livers of HF-fed rats showed greater conversion of alanine and pyruvate into carbohydrate than did control liver, although the rates were less than in HP-liver. Despite elevated gluconeogenesis in liver of HF-rats, plasma glucagon and insulin and liver cyclic AMP were normal. These findings demonstrate that some mechanism other than a rise in the level of glucagon is responsible for stimulating carbohydrate synthesis. We have postulated that acetyl CoA, which is formed in large amounts as a result of accelerated fatty acid oxidation, promotes gluconeogenesis in HF-fed rats. The observation that plasma glucagon is elevated in HP-fed but not in HF-fed rats demonstrates that protein intake and not carbohydrate restriction stimulates glucagon secretion since both diets are carbohydrate-free. Despite the lack of dietary carbohydrate, plasma glucose of HF-fed rats was normal and liver glycogen was about half that of controls. When HF animals were starved for twenty-four hours, mobilization of carbohydrate stores was diminished indicating that glucose utilization is reduced as a result of fat feeding.