Bernhard Breier - Academia.edu (original) (raw)

Papers by Bernhard Breier

Research paper thumbnail of The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat

Journal of Endocrinology

GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms ... more GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms of these harmful effects of GH are unknown but have been, in part, ascribed to interactions between GH and the immune system. Because GH has pattern-dependent actions we have now compared the dose-related effects of continuous and intermittent GH treatment given with or without an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals monitored for a further 16 h. LPS administration alone led to neutrophilia and lymphopoenia, with increased plasma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 microg/kg per day) followed by LPS c...

Research paper thumbnail of Predictors and risks of body fat profiles in young New Zealand European, Māori and Pacific women: study protocol for the women’s EXPLORE study

SpringerPlus, 2015

Background: Body mass index (BMI) (kg/m 2 ) is used internationally to assess body mass or adipos... more Background: Body mass index (BMI) (kg/m 2 ) is used internationally to assess body mass or adiposity. However, BMI does not discriminate body fat content or distribution and may vary among ethnicities. Many women with normal BMI are considered healthy, but may have an unidentified "hidden fat" profile associated with higher metabolic disease risk. If only BMI is used to indicate healthy body size, it may fail to predict underlying risks of diseases of lifestyle among population subgroups with normal BMI and different adiposity levels or distributions. Higher body fat levels are often attributed to excessive dietary intake and/or inadequate physical activity. These environmental influences regulate genes and proteins that alter energy expenditure/storage. Micro ribonucleic acid (miRNAs) can influence these genes and proteins, are sensitive to diet and exercise and may influence the varied metabolic responses observed between individuals. The study aims are to investigate associations between different body fat profiles and metabolic disease risk; dietary and physical activity patterns as predictors of body fat profiles; and whether these risk factors are associated with the expression of microRNAs related to energy expenditure or fat storage in young New Zealand women. Given the rising prevalence of obesity globally, this research will address a unique gap of knowledge in obesity research. Methods/Design: A cross-sectional design to investigate 675 NZ European, Māori, and Pacific women aged 16-45 years. Women are classified into three main body fat profiles (n = 225 per ethnicity; n = 75 per body fat profile): 1) normal BMI, normal body fat percentage (BF%); 2) normal BMI, high BF%; 3) high BMI, high BF%. Regional body composition, biomarkers of metabolic disease risk (i.e. fasting insulin, glucose, HbA1c, lipids), inflammation (i.e. IL-6, TNF-alpha, hs-CRP), associations between lifestyle factors (i.e. dietary intake, physical activity, taste perceptions) and microRNA expression will be investigated. Discussion: This research targets post-menarcheal, premenopausal women, potentially exhibiting lifestyle behaviours resulting in excess body fat affecting metabolic health. These behaviours may be characterised by specific patterns of microRNA expression that will be explored in terms of tailored solutions specific to body fat profile groups and ethnicities.

Research paper thumbnail of Pharmacokinetics of glycine–proline–glutamate, the N-terminal tripeptide of insulin-like growth factor-1, in rats

Analytical Biochemistry, 2003

Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and ... more Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and has been shown to be neuroprotective following ischemia-induced brain injury. The pharmacokinetics of GPE were studied in adult rats since GPE is a candidate for use in neuroprotection therapies. To measure plasma concentrations of GPE a novel radioimmunoassay was developed whereby GPE was initially derivatized with Bolton and Hunter reagent before use in a standard homologous assay against the Bolton and Hunter iodinated form. The derivatized GPE radioimmunoassay showed a 83% recovery of unlabeled GPE and complete parallel displacement with rat plasma. The simplicity and speed of the assay described here indicate an exciting new use for a previously described technology. The pharmacokinetic studies were conducted in adult rats using a single bolus intravenous injection of GPE at 30 or 100 mg/kg and showed that GPE was rapidly cleared from the circulation. In addition, evidence of the route of the metabolic degradation of GPE is presented. The findings presented here are the first description of the pharmacokinetics of GPE and suggest that, because of its very short half-life in plasma, continuous intravenous infusion of GPE may be the preferred route of administration for use in future neuroprotection therapies.

Research paper thumbnail of Fetal Growth Restriction and the Developmental Origins of Adult Disease Hypothesis: Experimental Studies and Biological Consequences

Pediatric and Adolescent Medicine, 2008

ABSTRACT The clinical term small for gestational age (SGA) is used to describe newborn infants wh... more ABSTRACT The clinical term small for gestational age (SGA) is used to describe newborn infants whose birth weight falls below the 10th percentile of weight for their gestational age. This classification encompasses two broad developmental phenotypes, infants which have achieved their genetic potential for growth but are constitutionally small, and infants that have experienced fetal growth restriction (FGR) and have failed to achieve their relative growth potential. The diagnosis of FGR has an immediate clinical relevance for SGA babies because FGR is associated with an increased risk of perinatal complications, including preventable neonatal mortality. Due to the serious nature of such perinatal complications there has been a great deal of interest in identifying and defining the immediate causes and consequences of FGR. Currently FGR is commonly described as a consequence of adverse prenatal environmental stimuli that can impair gas exchange and nutrient delivery to the fetus disrupting the normal patterns of growth and development. Placental dysfunction and adverse maternal factors such as, smoking, maternal disease and malnutrition are considered key pathological factors responsible for FGR. While the majority of clinical research has focused on the immediate neonatal consequences of FGR, recent research over the past 15 years suggests that FGR can adversely affect postnatal health outcomes well into adulthood. This concept is called the developmental origins of health and disease hypothesis (DOHaD).

Research paper thumbnail of Size at birth and plasma insulin-like growth factor-1 concentrations

Archives of Disease in Childhood, 1995

OBJECTIVE--To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like ... more OBJECTIVE--To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood. DESIGN--A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth. SETTING--Pune, India, and Salisbury, England. SUBJECTS--200 children born during

Research paper thumbnail of Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Journal of Endocrinology

Increasing evidence from human epidemiological studies suggests that poor growth before birth is ... more Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 microl), IGF-I (2 micrograms/g body weight) or GH (2 microgram...

Research paper thumbnail of Effects of dexamethasone and colostrum intake on the somatotropic axis in neonatal calves

American journal of physiology. Endocrinology and metabolism, 2003

Glucocorticoids and colostrum feeding influence postnatal maturation of the somatotropic axis. We... more Glucocorticoids and colostrum feeding influence postnatal maturation of the somatotropic axis. We have tested the hypothesis that dexamethasone (Dexa) affects the somatotropic axis in neonatal calves dependent on colostrum intake. Calves were fed either with colostrum or with a milk-based formula (n = 14/group), and, in each feeding group, one-half of the calves were treated with Dexa (30 micro g. kg body wt-1. day-1). Pre- and postprandial blood samples were taken on days 1, 2, 4, and 5, and liver samples were taken on day 5 of life. Dexa increased insulin-like growth factor (IGF)-I, but decreased growth hormone (GH) and IGF-binding protein (IGFBP)-1 and -2 plasma concentrations and increased GH receptor (GHR) mRNA levels in liver. Dexa increased IGF-I mRNA levels only in formula-fed calves and increased hepatic GHR binding capacity, but only in colostrum-fed calves. Colostrum feeding decreased IGFBP-1 and -2 plasma concentrations and hepatic IGFBP-2 and -3 mRNA levels. In conclusi...

Research paper thumbnail of Blood plasma concentrations of insulin-like growth factor-I (IGF-I) in resting standardbred horses

Veterinary journal (London, England : 1997), 2002

A survey of standardbred horses was conducted to build up a normal population profile for insulin... more A survey of standardbred horses was conducted to build up a normal population profile for insulin like growth factor-I (IGF-I) concentrations in racing standardbreds and to ascertain how age, sex and geographic location affect IGF-I. Blood samples were drawn by jugular venepuncture from 202 racing standardbred horses aged one to eight years located in five different geographic regions of New Zealand. IGF-I concentrations were determined by insulin like growth factor-I binding protein (IGFBP)-blocked radioimmunoassay validated for the horse. As described in other species, age played a significant (P<0.05) role in IGF-I concentrations with the highest concentrations occurring in the younger horses. There was a significant (P<0.05) sex effect, intact males having significantly higher IGF-I concentrations compared of mares and/or geldings. Geographic location had a significant (P<0.05) influence on IGF-I. A significant (P<0.05) trainer effect also was noted both within and b...

Research paper thumbnail of High-fat diets rich in ω-3 or ω-6 polyunsaturated fatty acids have distinct effects on lipid profiles and lipid peroxidation in mice selected for either high body weight or leanness

Nutrition, 2013

Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the... more Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of micedhigh body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in u-3 or u-6 polyunsaturated fatty acids (PUFA). Methods: The isocaloric HFDs were enriched with either u-3 PUFA (27% fish oil, u-3 HFD) or u-6 PUFA (27% sunflower oil, u-6 HFD), and the control group was fed standard chow (7.2% fat).

Research paper thumbnail of Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity

Physiological genomics, Jan 15, 2014

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silenc... more Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA ...

Research paper thumbnail of Elevating Maternal Insulin-Like Growth Factor-I in Mice and Rats Alters the Pattern of Fetal Growth by Removing Maternal Constraint

Journal of Endocrinology, 1992

Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the ... more Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Growth hormone or insulin-like growth factor-I extends longevity of equine spermatozoa in vitro

Theriogenology, 2002

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and... more Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and IGF-I has been measured in epididymal¯uid and seminal plasma. This study was designed to investigate the direct effects of GH or IGF-I on the motility of mature equine spermatozoa in vitro. We compared the effects of one concentration (100 ng/ml) of recombinant bovine GH (rbGH) and recombinant human IGF-I (rhIGF-I) on motility and motion characteristics of equine spermatozoa over a 24 h period. Motility was maintained longer in spermatozoa treated with either rbGH or rhIGF-I during a 24 h period at room temperature (P < 0:05). Spermatozoa motion characteristics at time 0, 1, 2, 4, 6, 12 and 24 h for both rbGH and rhIGF-I were not signi®cantly different from the respective controls.

Research paper thumbnail of The Effects of Bovine Recombinant Growth Hormone Administration on Insulin-like Growth Factor-I and the Haemopoietic System in Thoroughbred Geldings

The Veterinary Journal, 2000

The effect of intramuscularly administered recombinant bovine growth hormone (rbGH) on insulin-li... more The effect of intramuscularly administered recombinant bovine growth hormone (rbGH) on insulin-like growth factor-I (IGF-I) and white and red blood cell indices was studied in Thoroughbred geldings. An insulin-like growth factor binding protein (IGFBP)-blocked radioimmunoassay was modified and validated for the measurement of IGF-I in equine blood plasma. Baseline values of IGF-I and blood indices were determined over a 48 h period and then a single dose of 5 µg/kg, 10 µg/kg or 50 µg/kg of rbGH was administered. Insulin-like growth factor-I levels increased in a dose-dependent manner, with the highest values between 12 h and 24 h. The highest dose (50 µg/kg) yielded the greatest IGF-I response with a 90.2 ± 10.8% increase at 24 h. White blood cell count increased following the three doses of rbGH with the highest white blood cell count at 12 h after the 50 µg/kg dose. Haemoglobin was significantly increased at 24 h (P < 0.05), when values following doses of 10 µg/kg and 50 µg/kg were significantly greater than after the vehicle or the dose of 5 µg/kg. Red blood cell count was not affected by any of the rbGH doses. These results indicated that rbGH is biologically active in the horse and that rbGH at a dose rate of 10 µg/kg or more could be used therapeutically.

Research paper thumbnail of Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep

The Journal of Physiology, 2001

Research paper thumbnail of Morphological changes in the oesophagus of newborn pigs: effects of age, diet and oral insulin-like growth factor I (IGF-I) or IGF-II

Reproduction, Fertility and Development, 1996

It has been reported in the literature that the stomach and the intestine in newborns undergo pro... more It has been reported in the literature that the stomach and the intestine in newborns undergo profound growth and functional maturation during the immediate postnatal period and diet ingestion has a significant impact on these changes. The present paper examines oesophageal development in newborn pigs during the first three postnatal days and the effects of diet and oral insulin-like growth factor I (IGF-I) or IGF-II on oesophageal morphology. It was observed that marked changes, including reduction in thickness of the epithelium, accelerated proliferation and migration of basal epithelial cells and increased accumulation of mucus in the glandular cells, occurred during the first postnatal day following onset of natural suckling. Bottle-feeding with various liquid diets (i.e. porcine colostrum, bovine colostrum, bovine milk, and infant milk formula), induced marked morphological changes which were similar to those induced by natural suckling. However, bottle-feeding with water did not result in marked reduction in the thickness of the epithelium nor did it accelerate basal epithelial cell proliferation and migration. Oral IGF-I, but not IGF-II, increased basal epithelial cell proliferation up to 81%. Owing to a large inter-animal variation, the increment did not reach a significant level (P = 0.071). The results suggest that chemical constituents in the diet and physical stimulation of food ingestion, which cause sloughing off of luminal surface tissue, are two major stimuli or epithelial cell proliferation in the new born oesophagus.

Research paper thumbnail of Influence of fetal and maternal genotype for circulating insulin-like growth factor I on fetal growth in mice

Reproduction, 1994

The role of insulin-like growth factor I in the regulation of fetal growth was investigated in tw... more The role of insulin-like growth factor I in the regulation of fetal growth was investigated in two lines of mice selected for high or low concentrations of this factor in plasma. In Expt 1, females from each line were mated with males of the reciprocal line to generate fetuses of equivalent genotype. Females with low concentration of the factor in plasma exhibited the typical negative relationship between mean fetal mass and litter size (b = \ m=-\ 0.032 \ m=+-\ 0.006 g per fetus, P < 0.01). However, dams of the line with high concentrations of the factor did not exhibit this relationship (b = \m=-\0.004 \ m=+-\ 0.006 g per fetus), despite the fact that they had 26% larger litters (P < 0.05) at a common maternal body mass. This difference in maternal constraint apparently reflects a greater capacity for nutrient transfer to the fetuses in the dams with more insulin-like growth factor I in plasma, as suggested by the absence of a relationship between mean placental mass and mean fetal mass in that line. In Expt 2, the effect of fetal genotype for insulin-like growth factor I was investigated by transferring embryos of the two lines into females of an unrelated strain. Fetuses from the line with high concentrations of the factor in plasma were heavier at term (1.51 versus 1.37 g, pooled SE = 0.05 g, P < 0.05) than fetuses from the line with low concentrations in plasma. It is therefore concluded that fetal growth is influenced by both the maternal and fetal genotypes for insulin-like growth factor I, but in qualitatively different manners.

Research paper thumbnail of Reproductive performance and fetal growth in female mice from lines divergently selected on the basis of plasma IGF-1 concentrations

Reproduction, 1989

Reproductive performance, mammary gland weight and plasma concentrations of insulin-like growth f... more Reproductive performance, mammary gland weight and plasma concentrations of insulin-like growth factor-1 (IGF-1) were examined in 18-day-pregnant mice from lines divergently selected on the basis of plasma IGF-1 concentration. Females ofthe high IGF-1 (H) line were 14% heavier than those of the low IGF-1 (L) line at mating but did not differ in conception rate during a 15-day mating period. H-line females produced significantly larger litters by an average of 1 \ m=. \ 5fetuses (19%), heavier fetuses (7%), greater total fetal weight (30%), heavier placental discs (15%), greater total placental weight (35%) and heavier mammary glands (18%). Plasma IGF-1 values were 12% greater in H\ x=r eq-\ line than L-line females at Day 19 of gestation but the line difference was not significant. It is concluded that differences between the lines in litter size and mammary gland weight are most likely due to differences in maternal bodyweight (which are in turn a consequence of selection for plasma IGF-1 at puberty). Whether the difference in fetal weight is a function of fetal capacity to grow in utero or ability of the dam to provide nutrients for fetal growth is yet to be determined.

Research paper thumbnail of Chronic Maternal Undernutrition in the Rat Leads to Delayed Postnatal Growth and Elevated Blood Pressure of Offspring

Pediatric Research, 1996

To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood... more To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p &amp;amp;lt; 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

Research paper thumbnail of Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

Nutrition & Metabolism, 2011

Background: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) co... more Background: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.

Research paper thumbnail of Effects of Oral IGF-I or IGF-II on Digestive Organ Growth in Newborn Piglets

Neonatology, 1994

To study whether colostrum-borne growth factors are responsible for the rapid GI tissue growth in... more To study whether colostrum-borne growth factors are responsible for the rapid GI tissue growth in naturally suckled newborn animals, newborn unsuckled piglets were bottle-fed for 24 h with infant milk formula with or without addition of 2 micrograms/ml of recombinant human insulin-like growth factor-I (IGF-I) or insulin-like growth factor-II (IGF-II), a level which approximated that of porcine colostrum. The animals were then sacrificed for measurements of their digestive organ weights and contents of protein, RNA and DNA in the organs. The treatment with IGF-I or IGF-II failed to show any significant effect on the weight of the esophagus, stomach, small intestine, large intestine, mandibular glands, kidneys and the spleen, and had no effects on the contents of protein, RNA and DNA in the small intestinal mucosa, the liver and the spleen. However, piglets fed with infant formula containing IGF-I (n = 7) or IGF-II (n = 7) had a heavier pancreas (p &amp;amp;lt; 0.05) compared to formula-fed controls (n = 7). The DNA content in the stomach and the pancreas were greater in animals treated with IGF-I or IGF-II than in controls. Using a cell labelling technique it was shown that both IGF-I and IGF-II stimulated cell proliferation in the small intestinal crypts. The results indicate that the substantial GI tissue growth reported in newborn animals is unlikely due to colostrum-borne IGF-I or IGF-II alone. On the other hand the study does suggest that oral IGF-I and IGF-II are capable of stimulating cell proliferation in the GI tract.

Research paper thumbnail of The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat

Journal of Endocrinology

GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms ... more GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms of these harmful effects of GH are unknown but have been, in part, ascribed to interactions between GH and the immune system. Because GH has pattern-dependent actions we have now compared the dose-related effects of continuous and intermittent GH treatment given with or without an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals monitored for a further 16 h. LPS administration alone led to neutrophilia and lymphopoenia, with increased plasma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 microg/kg per day) followed by LPS c...

Research paper thumbnail of Predictors and risks of body fat profiles in young New Zealand European, Māori and Pacific women: study protocol for the women’s EXPLORE study

SpringerPlus, 2015

Background: Body mass index (BMI) (kg/m 2 ) is used internationally to assess body mass or adipos... more Background: Body mass index (BMI) (kg/m 2 ) is used internationally to assess body mass or adiposity. However, BMI does not discriminate body fat content or distribution and may vary among ethnicities. Many women with normal BMI are considered healthy, but may have an unidentified "hidden fat" profile associated with higher metabolic disease risk. If only BMI is used to indicate healthy body size, it may fail to predict underlying risks of diseases of lifestyle among population subgroups with normal BMI and different adiposity levels or distributions. Higher body fat levels are often attributed to excessive dietary intake and/or inadequate physical activity. These environmental influences regulate genes and proteins that alter energy expenditure/storage. Micro ribonucleic acid (miRNAs) can influence these genes and proteins, are sensitive to diet and exercise and may influence the varied metabolic responses observed between individuals. The study aims are to investigate associations between different body fat profiles and metabolic disease risk; dietary and physical activity patterns as predictors of body fat profiles; and whether these risk factors are associated with the expression of microRNAs related to energy expenditure or fat storage in young New Zealand women. Given the rising prevalence of obesity globally, this research will address a unique gap of knowledge in obesity research. Methods/Design: A cross-sectional design to investigate 675 NZ European, Māori, and Pacific women aged 16-45 years. Women are classified into three main body fat profiles (n = 225 per ethnicity; n = 75 per body fat profile): 1) normal BMI, normal body fat percentage (BF%); 2) normal BMI, high BF%; 3) high BMI, high BF%. Regional body composition, biomarkers of metabolic disease risk (i.e. fasting insulin, glucose, HbA1c, lipids), inflammation (i.e. IL-6, TNF-alpha, hs-CRP), associations between lifestyle factors (i.e. dietary intake, physical activity, taste perceptions) and microRNA expression will be investigated. Discussion: This research targets post-menarcheal, premenopausal women, potentially exhibiting lifestyle behaviours resulting in excess body fat affecting metabolic health. These behaviours may be characterised by specific patterns of microRNA expression that will be explored in terms of tailored solutions specific to body fat profile groups and ethnicities.

Research paper thumbnail of Pharmacokinetics of glycine–proline–glutamate, the N-terminal tripeptide of insulin-like growth factor-1, in rats

Analytical Biochemistry, 2003

Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and ... more Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and has been shown to be neuroprotective following ischemia-induced brain injury. The pharmacokinetics of GPE were studied in adult rats since GPE is a candidate for use in neuroprotection therapies. To measure plasma concentrations of GPE a novel radioimmunoassay was developed whereby GPE was initially derivatized with Bolton and Hunter reagent before use in a standard homologous assay against the Bolton and Hunter iodinated form. The derivatized GPE radioimmunoassay showed a 83% recovery of unlabeled GPE and complete parallel displacement with rat plasma. The simplicity and speed of the assay described here indicate an exciting new use for a previously described technology. The pharmacokinetic studies were conducted in adult rats using a single bolus intravenous injection of GPE at 30 or 100 mg/kg and showed that GPE was rapidly cleared from the circulation. In addition, evidence of the route of the metabolic degradation of GPE is presented. The findings presented here are the first description of the pharmacokinetics of GPE and suggest that, because of its very short half-life in plasma, continuous intravenous infusion of GPE may be the preferred route of administration for use in future neuroprotection therapies.

Research paper thumbnail of Fetal Growth Restriction and the Developmental Origins of Adult Disease Hypothesis: Experimental Studies and Biological Consequences

Pediatric and Adolescent Medicine, 2008

ABSTRACT The clinical term small for gestational age (SGA) is used to describe newborn infants wh... more ABSTRACT The clinical term small for gestational age (SGA) is used to describe newborn infants whose birth weight falls below the 10th percentile of weight for their gestational age. This classification encompasses two broad developmental phenotypes, infants which have achieved their genetic potential for growth but are constitutionally small, and infants that have experienced fetal growth restriction (FGR) and have failed to achieve their relative growth potential. The diagnosis of FGR has an immediate clinical relevance for SGA babies because FGR is associated with an increased risk of perinatal complications, including preventable neonatal mortality. Due to the serious nature of such perinatal complications there has been a great deal of interest in identifying and defining the immediate causes and consequences of FGR. Currently FGR is commonly described as a consequence of adverse prenatal environmental stimuli that can impair gas exchange and nutrient delivery to the fetus disrupting the normal patterns of growth and development. Placental dysfunction and adverse maternal factors such as, smoking, maternal disease and malnutrition are considered key pathological factors responsible for FGR. While the majority of clinical research has focused on the immediate neonatal consequences of FGR, recent research over the past 15 years suggests that FGR can adversely affect postnatal health outcomes well into adulthood. This concept is called the developmental origins of health and disease hypothesis (DOHaD).

Research paper thumbnail of Size at birth and plasma insulin-like growth factor-1 concentrations

Archives of Disease in Childhood, 1995

OBJECTIVE--To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like ... more OBJECTIVE--To test the hypothesis that reduced fetal growth leads to altered plasma insulin-like growth factor-1 (IGF-1) concentrations in childhood. DESIGN--A follow up study of 4 year old children whose birth weights were recorded, and of 7 year old children whose weight, length, head circumference, and placental weight were measured at birth. SETTING--Pune, India, and Salisbury, England. SUBJECTS--200 children born during

Research paper thumbnail of Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Journal of Endocrinology

Increasing evidence from human epidemiological studies suggests that poor growth before birth is ... more Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 microl), IGF-I (2 micrograms/g body weight) or GH (2 microgram...

Research paper thumbnail of Effects of dexamethasone and colostrum intake on the somatotropic axis in neonatal calves

American journal of physiology. Endocrinology and metabolism, 2003

Glucocorticoids and colostrum feeding influence postnatal maturation of the somatotropic axis. We... more Glucocorticoids and colostrum feeding influence postnatal maturation of the somatotropic axis. We have tested the hypothesis that dexamethasone (Dexa) affects the somatotropic axis in neonatal calves dependent on colostrum intake. Calves were fed either with colostrum or with a milk-based formula (n = 14/group), and, in each feeding group, one-half of the calves were treated with Dexa (30 micro g. kg body wt-1. day-1). Pre- and postprandial blood samples were taken on days 1, 2, 4, and 5, and liver samples were taken on day 5 of life. Dexa increased insulin-like growth factor (IGF)-I, but decreased growth hormone (GH) and IGF-binding protein (IGFBP)-1 and -2 plasma concentrations and increased GH receptor (GHR) mRNA levels in liver. Dexa increased IGF-I mRNA levels only in formula-fed calves and increased hepatic GHR binding capacity, but only in colostrum-fed calves. Colostrum feeding decreased IGFBP-1 and -2 plasma concentrations and hepatic IGFBP-2 and -3 mRNA levels. In conclusi...

Research paper thumbnail of Blood plasma concentrations of insulin-like growth factor-I (IGF-I) in resting standardbred horses

Veterinary journal (London, England : 1997), 2002

A survey of standardbred horses was conducted to build up a normal population profile for insulin... more A survey of standardbred horses was conducted to build up a normal population profile for insulin like growth factor-I (IGF-I) concentrations in racing standardbreds and to ascertain how age, sex and geographic location affect IGF-I. Blood samples were drawn by jugular venepuncture from 202 racing standardbred horses aged one to eight years located in five different geographic regions of New Zealand. IGF-I concentrations were determined by insulin like growth factor-I binding protein (IGFBP)-blocked radioimmunoassay validated for the horse. As described in other species, age played a significant (P<0.05) role in IGF-I concentrations with the highest concentrations occurring in the younger horses. There was a significant (P<0.05) sex effect, intact males having significantly higher IGF-I concentrations compared of mares and/or geldings. Geographic location had a significant (P<0.05) influence on IGF-I. A significant (P<0.05) trainer effect also was noted both within and b...

Research paper thumbnail of High-fat diets rich in ω-3 or ω-6 polyunsaturated fatty acids have distinct effects on lipid profiles and lipid peroxidation in mice selected for either high body weight or leanness

Nutrition, 2013

Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the... more Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of micedhigh body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in u-3 or u-6 polyunsaturated fatty acids (PUFA). Methods: The isocaloric HFDs were enriched with either u-3 PUFA (27% fish oil, u-3 HFD) or u-6 PUFA (27% sunflower oil, u-6 HFD), and the control group was fed standard chow (7.2% fat).

Research paper thumbnail of Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity

Physiological genomics, Jan 15, 2014

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silenc... more Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA ...

Research paper thumbnail of Elevating Maternal Insulin-Like Growth Factor-I in Mice and Rats Alters the Pattern of Fetal Growth by Removing Maternal Constraint

Journal of Endocrinology, 1992

Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the ... more Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Growth hormone or insulin-like growth factor-I extends longevity of equine spermatozoa in vitro

Theriogenology, 2002

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and... more Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and IGF-I has been measured in epididymal¯uid and seminal plasma. This study was designed to investigate the direct effects of GH or IGF-I on the motility of mature equine spermatozoa in vitro. We compared the effects of one concentration (100 ng/ml) of recombinant bovine GH (rbGH) and recombinant human IGF-I (rhIGF-I) on motility and motion characteristics of equine spermatozoa over a 24 h period. Motility was maintained longer in spermatozoa treated with either rbGH or rhIGF-I during a 24 h period at room temperature (P < 0:05). Spermatozoa motion characteristics at time 0, 1, 2, 4, 6, 12 and 24 h for both rbGH and rhIGF-I were not signi®cantly different from the respective controls.

Research paper thumbnail of The Effects of Bovine Recombinant Growth Hormone Administration on Insulin-like Growth Factor-I and the Haemopoietic System in Thoroughbred Geldings

The Veterinary Journal, 2000

The effect of intramuscularly administered recombinant bovine growth hormone (rbGH) on insulin-li... more The effect of intramuscularly administered recombinant bovine growth hormone (rbGH) on insulin-like growth factor-I (IGF-I) and white and red blood cell indices was studied in Thoroughbred geldings. An insulin-like growth factor binding protein (IGFBP)-blocked radioimmunoassay was modified and validated for the measurement of IGF-I in equine blood plasma. Baseline values of IGF-I and blood indices were determined over a 48 h period and then a single dose of 5 µg/kg, 10 µg/kg or 50 µg/kg of rbGH was administered. Insulin-like growth factor-I levels increased in a dose-dependent manner, with the highest values between 12 h and 24 h. The highest dose (50 µg/kg) yielded the greatest IGF-I response with a 90.2 ± 10.8% increase at 24 h. White blood cell count increased following the three doses of rbGH with the highest white blood cell count at 12 h after the 50 µg/kg dose. Haemoglobin was significantly increased at 24 h (P < 0.05), when values following doses of 10 µg/kg and 50 µg/kg were significantly greater than after the vehicle or the dose of 5 µg/kg. Red blood cell count was not affected by any of the rbGH doses. These results indicated that rbGH is biologically active in the horse and that rbGH at a dose rate of 10 µg/kg or more could be used therapeutically.

Research paper thumbnail of Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep

The Journal of Physiology, 2001

Research paper thumbnail of Morphological changes in the oesophagus of newborn pigs: effects of age, diet and oral insulin-like growth factor I (IGF-I) or IGF-II

Reproduction, Fertility and Development, 1996

It has been reported in the literature that the stomach and the intestine in newborns undergo pro... more It has been reported in the literature that the stomach and the intestine in newborns undergo profound growth and functional maturation during the immediate postnatal period and diet ingestion has a significant impact on these changes. The present paper examines oesophageal development in newborn pigs during the first three postnatal days and the effects of diet and oral insulin-like growth factor I (IGF-I) or IGF-II on oesophageal morphology. It was observed that marked changes, including reduction in thickness of the epithelium, accelerated proliferation and migration of basal epithelial cells and increased accumulation of mucus in the glandular cells, occurred during the first postnatal day following onset of natural suckling. Bottle-feeding with various liquid diets (i.e. porcine colostrum, bovine colostrum, bovine milk, and infant milk formula), induced marked morphological changes which were similar to those induced by natural suckling. However, bottle-feeding with water did not result in marked reduction in the thickness of the epithelium nor did it accelerate basal epithelial cell proliferation and migration. Oral IGF-I, but not IGF-II, increased basal epithelial cell proliferation up to 81%. Owing to a large inter-animal variation, the increment did not reach a significant level (P = 0.071). The results suggest that chemical constituents in the diet and physical stimulation of food ingestion, which cause sloughing off of luminal surface tissue, are two major stimuli or epithelial cell proliferation in the new born oesophagus.

Research paper thumbnail of Influence of fetal and maternal genotype for circulating insulin-like growth factor I on fetal growth in mice

Reproduction, 1994

The role of insulin-like growth factor I in the regulation of fetal growth was investigated in tw... more The role of insulin-like growth factor I in the regulation of fetal growth was investigated in two lines of mice selected for high or low concentrations of this factor in plasma. In Expt 1, females from each line were mated with males of the reciprocal line to generate fetuses of equivalent genotype. Females with low concentration of the factor in plasma exhibited the typical negative relationship between mean fetal mass and litter size (b = \ m=-\ 0.032 \ m=+-\ 0.006 g per fetus, P < 0.01). However, dams of the line with high concentrations of the factor did not exhibit this relationship (b = \m=-\0.004 \ m=+-\ 0.006 g per fetus), despite the fact that they had 26% larger litters (P < 0.05) at a common maternal body mass. This difference in maternal constraint apparently reflects a greater capacity for nutrient transfer to the fetuses in the dams with more insulin-like growth factor I in plasma, as suggested by the absence of a relationship between mean placental mass and mean fetal mass in that line. In Expt 2, the effect of fetal genotype for insulin-like growth factor I was investigated by transferring embryos of the two lines into females of an unrelated strain. Fetuses from the line with high concentrations of the factor in plasma were heavier at term (1.51 versus 1.37 g, pooled SE = 0.05 g, P < 0.05) than fetuses from the line with low concentrations in plasma. It is therefore concluded that fetal growth is influenced by both the maternal and fetal genotypes for insulin-like growth factor I, but in qualitatively different manners.

Research paper thumbnail of Reproductive performance and fetal growth in female mice from lines divergently selected on the basis of plasma IGF-1 concentrations

Reproduction, 1989

Reproductive performance, mammary gland weight and plasma concentrations of insulin-like growth f... more Reproductive performance, mammary gland weight and plasma concentrations of insulin-like growth factor-1 (IGF-1) were examined in 18-day-pregnant mice from lines divergently selected on the basis of plasma IGF-1 concentration. Females ofthe high IGF-1 (H) line were 14% heavier than those of the low IGF-1 (L) line at mating but did not differ in conception rate during a 15-day mating period. H-line females produced significantly larger litters by an average of 1 \ m=. \ 5fetuses (19%), heavier fetuses (7%), greater total fetal weight (30%), heavier placental discs (15%), greater total placental weight (35%) and heavier mammary glands (18%). Plasma IGF-1 values were 12% greater in H\ x=r eq-\ line than L-line females at Day 19 of gestation but the line difference was not significant. It is concluded that differences between the lines in litter size and mammary gland weight are most likely due to differences in maternal bodyweight (which are in turn a consequence of selection for plasma IGF-1 at puberty). Whether the difference in fetal weight is a function of fetal capacity to grow in utero or ability of the dam to provide nutrients for fetal growth is yet to be determined.

Research paper thumbnail of Chronic Maternal Undernutrition in the Rat Leads to Delayed Postnatal Growth and Elevated Blood Pressure of Offspring

Pediatric Research, 1996

To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood... more To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p &amp;amp;lt; 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

Research paper thumbnail of Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

Nutrition & Metabolism, 2011

Background: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) co... more Background: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.

Research paper thumbnail of Effects of Oral IGF-I or IGF-II on Digestive Organ Growth in Newborn Piglets

Neonatology, 1994

To study whether colostrum-borne growth factors are responsible for the rapid GI tissue growth in... more To study whether colostrum-borne growth factors are responsible for the rapid GI tissue growth in naturally suckled newborn animals, newborn unsuckled piglets were bottle-fed for 24 h with infant milk formula with or without addition of 2 micrograms/ml of recombinant human insulin-like growth factor-I (IGF-I) or insulin-like growth factor-II (IGF-II), a level which approximated that of porcine colostrum. The animals were then sacrificed for measurements of their digestive organ weights and contents of protein, RNA and DNA in the organs. The treatment with IGF-I or IGF-II failed to show any significant effect on the weight of the esophagus, stomach, small intestine, large intestine, mandibular glands, kidneys and the spleen, and had no effects on the contents of protein, RNA and DNA in the small intestinal mucosa, the liver and the spleen. However, piglets fed with infant formula containing IGF-I (n = 7) or IGF-II (n = 7) had a heavier pancreas (p &amp;amp;lt; 0.05) compared to formula-fed controls (n = 7). The DNA content in the stomach and the pancreas were greater in animals treated with IGF-I or IGF-II than in controls. Using a cell labelling technique it was shown that both IGF-I and IGF-II stimulated cell proliferation in the small intestinal crypts. The results indicate that the substantial GI tissue growth reported in newborn animals is unlikely due to colostrum-borne IGF-I or IGF-II alone. On the other hand the study does suggest that oral IGF-I and IGF-II are capable of stimulating cell proliferation in the GI tract.