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Biomedical subjects

Ian D Caterson

Publications and source records attributed to Ian D Caterson.

18 recordsLinked to original sources
PubMed2006

Insulin resistance does not influence gene expression in skeletal muscle.

Insulin resistance is commonly observed in patients prior to the development of type 2 diabetes and may predict the onset of the disease. We tested the hypothesis that impairment in insulin stimulated glucose-disposal in insulin resistant patients would be reflected in the gene expression profile of skeletal muscle. We performed gene expression profiling on skeletal muscle of insulin resistant and insulin sensitive subjects using microarrays. Microarray analysis of 19,000 genes in skeletal muscle did not display a significant difference between insulin resistant and insulin sensitive muscle. This was confirmed with real-time PCR. Our results suggest that insulin resistance is not reflected by changes in the gene expression profile in skeletal muscle.

Adult↗
PubMed2006

Maternal undernutrition reduces aortic wall thickness and elastin content in offspring rats without altering endothelial function.

Epidemiological studies suggest a link between fetal/early infant nutrition and adult coronary artery disease. In the present study, we examined the effects of altering nutrition during gestation, lactation and juvenile life on aortic structure and function in rats. Wistar rat dams were fed either a control or low-protein diet throughout pregnancy, or a low-protein diet for the final 7 days of gestation only. At 21 days post-partum, male pups were weaned on to a control, low-protein or high-fat diet. At 12 weeks, the offspring rats were killed. In 46 rats, aortic sections were mounted and stained to assess media thickness and elastin content. In a further 38 rats, aortic rings were suspended in an organ bath and vascular reactivity was tested with dose-response curves to the endothelium-dependent dilator acetylcholine and the endothelium-independent dilator sodium nitroprusside. Rats exposed to maternal protein restriction while in utero had a significantly decreased aortic wall thickness compared with control rats (P=0.005). Total elastin content of the aorta was also decreased by both maternal low-protein (P=0.02) and early postnatal low-protein (P=0.01) diets. Neither maternal nor postnatal low-protein or high-fat diets, however, resulted in any significant changes in arterial dilator function. In conclusion, fetal undernutrition in rats, induced via a maternal low-protein diet, causes a decrease in aortic wall thickness and elastin content without altering aortic dilator function. These changes in vascular structure may amplify aging-related changes to the vasculature and contribute to the pathophysiology of the putative link between impaired fetal growth and adult cardiovascular disease.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Obesity and risk of low self-esteem: a statewide survey of Australian children.

OBJECTIVE: There is variation in the psychological distress associated with child obesity. Low self-esteem, when observed, provides very little information about the nature of the distress and no indication of the proportion of obese children affected. This study used a domain approach to self-competence to evaluate self-esteem in a representative sample of Australian children. PARTICIPANTS AND METHODS: A total of 2813 children (mean age: 11.3 years) took part in the study. They were recruited from 55 schools and were all in the last 2 years of primary school. Participants completed the Self-perception Profile for Children, a measure of body shape perception, and their height and weight were measured. RESULTS: Obese children had significantly lower perceived athletic competence, physical appearance, and global self-worth than their normal weight peers. Obese girls scored lower in these domains than obese boys and also had reduced perceived social acceptance. Obese children were 2-4 times more likely than their normal weight peers to have low domain competence. In terms of prevalence, 1 of 3 obese boys and 2 of 3 obese girls had low appearance competence, and 10% and 20%, respectively, had low global self-worth. Body dissatisfaction mediated most of the association between BMI and low competence in boys but not in girls. CONCLUSIONS: Obesity impacts the self-perception of children entering adolescence, especially in girls, but in selected areas of competence. Obese children are at particular risk of low perceived competence in sports, physical appearance, and peer engagement. Not all obese children are affected, although the reasons for their resilience are unclear. Quantifying risk of psychological distress alongside biomedical risk should help in arguing for more resources in child obesity treatment.

Adolescent↗
PubMed2006

Emerging pharmacotherapy for treating obesity and associated cardiometabolic risk.

The global obesity epidemic is causing much concern among health professionals due to the major health risks associated with obesity. Excess weight, particularly abdominal obesity, elevates multiple cardiovascular and metabolic risk factors, including Type 2 diabetes, hypertension, dyslipidaemia and cardiovascular disease. Thus obesity management goals should encompass health improvement and cardiometabolic risk reduction as well as weight loss. While lifestyle and diet modification form the basis of all effective strategies for weight reduction, some individuals may need additional intervention. About one in four people with BMI >27 kg/m(2) (those who have weight-related morbidity and who have been unsuccessful losing weight in standard ways) may require adjunctive therapy such as pharmacotherapy, very low energy diets/meal replacements, or bariatric surgery. This review focuses on appropriate use of pharmacotherapy for obesity and cardiometabolic risk. Sibutramine and orlistat are currently available for use in Australia. Rimonabant has been approved for use in the European Union, and is being considered for regulatory approval in the USA and Australia. The efficacy and safety of these three agents are examined. In addition, several novel pharmacotherapy agents in development are discussed.

Anti-Obesity Agents↗
PubMed2005

Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells.

1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 +/- 4 and 117 +/- 13% compared with controls, respectively; both P <or= 0.01). Ghrelin also increased ICAM-1 expression (119 +/- 17% of control; P <or= 0.01). 5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values. 6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression. 7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader-Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.

Cell Adhesion↗
PubMed2004

Resting metabolic rate in severely obese diabetic and nondiabetic subjects.

OBJECTIVES: To compare the resting metabolic rate (RMR) between diabetic and nondiabetic obese subjects and to develop a predictive equation of RMR for these subjects. RESEARCH METHODS AND PROCEDURES: Obese adults (1088; mean age = 44.9 +/- 12.7 years) with BMI > or = 35 kg/m2 (mean BMI = 46.4 +/- 8.4 kg/m2) were recruited. One hundred forty-two subjects (61 men, 81 women) were diagnosed with type 2 diabetes (DM), giving the prevalence of DM in this clinic population as 13.7%. RMR was measured by indirect calorimetry, and several multivariate linear regression models were performed using age, gender, weight, height, BMI, fat mass, fat mass percentage, and fat-free mass as independent variables. RESULTS: The severely obese patients with DM had consistently higher RMR after adjustment for all other variables. The best predictive equation for the severely obese was RMR = 71.767 - 2.337 x age + 257.293 x gender (women = 0 and men = 1) + 9.996 x weight (in kilograms) + 4.132 x height (in centimeters) + 145.959 x DM (nondiabetic = 0 and diabetic = 1). The age, weight, and height-adjusted least square means of RMR between diabetic and nondiabetic groups were significantly different in both genders. DISCUSSION: Severely obese patients with type 2 diabetes had higher RMR than those without diabetes. The RMR of severely obese subjects was best predicted by an equation using age, gender, weight, height, and DM as variables.

Adult↗
PubMed2003

Maternal protein restriction increases hepatic glycogen storage in young rats.

This study aimed to determine whether maternal protein restriction alters hepatic glycogen metabolism. Mated female rats were fed diets containing 20% protein throughout pregnancy and lactation (CONT), 8% protein throughout pregnancy and lactation (LP), or 8% protein during the last week of pregnancy only and lactation (LLP). Weights and lengths were reduced in the LLP and LP offspring compared with the CONT offspring. The LLP and LP offspring demonstrated reduced insulin concentrations at both 10 and 26 d and also failed to show the increase in insulin seen with time in the CONT offspring. Serum glucose and leptin levels increased with time but were not different among the groups; however, in relation to adiposity leptin levels were greater in the LLP and LP offspring at 26 d. The LLP and LP offspring had increased hepatic glycogen at day 10 (CONT, 75.1 +/- 9.8; LLP, 103.4 +/- 11.0; LP, 116.0 +/- 18.4 glucose residues/g tissue) and d 26 (CONT, 183.1 +/- 38.9; LLP, 395.3 +/- 16.8; LP, 396.6 +/- 15.1 glucose residues/g tissue). Glycogen synthase expression was increased in the LLP and LP offspring at 10 d but not 26 d; glucose transporter 2 and glycogen phosphorylase expressions were not different at either time. At 26 d glycogen synthase activity was not different; however, glycogen phosphorylase a activity was reduced. The enhanced capacity to store glycogen despite reductions in insulin secretion suggests increased insulin sensitivity possibly acting with an alternative non-insulin-dependent glycogen storage mechanism.

Adipose Tissue↗
PubMed2003

Association of obesity, but not diabetes or hypertension, with glucocorticoid receptor N363S variant.

OBJECTIVE: To determine whether the N363S variant in the glucocorticoid receptor (encoded by nuclear receptor subfamily 3, group C, member 1: NR3C1) is associated with obesity, type 2 diabetes, or hypertension. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional case-control study involving 951 Anglo-Celtic/Northern European subjects from Sydney. This study consisted of the following: 1) an obesity clinic group, most of whom had "morbid obesity" (mean BMI for group = 43 +/- 8 kg/m(2); n = 152); 2) a type 2 diabetes clinic group (n = 356); 3) patients with essential hypertension who had a strong family history (n = 141); and 4) normal healthy controls (n = 302). N363S genotype, BMI, and a range of other parameters relevant to each group were measured. RESULTS: Compared with the frequency of 0.04 in nonobese healthy subjects, the S363 allele was significantly higher in obesity clinic patients (0.17; p = 5.6 x 10(-8)), subjects with diabetes who were also obese (0.09; p = 0.0045), subjects with hypertension who were also overweight (0.08; p = 0.0016), and overweight healthy subjects (0.12; p = 0.0004). DISCUSSION: The NR3C1 N363S variant is associated with obesity and overweight in a range of patient settings but is not associated with hypertension or type 2 diabetes.

Adult↗
PubMed2003

Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed to a low-protein diet in utero.

OBJECTIVE: Intrauterine growth restriction is associated with increased prevalence of the metabolic syndrome in adult life, including increased adiposity. The aim of this study was to investigate if maternal protein energy malnutrition is associated with changes in expression of genes involved in fat partitioning in weanling rats. RESEARCH METHODS AND PROCEDURES: Time-mated mothers were placed on one of two isocaloric diets, low protein [(LP), 8% protein] or control (20% protein). All mothers remained on the diet throughout pregnancy and lactation. A third group received control for 2 weeks and was switched to LP for the last week of pregnancy and lactation [late low protein (LLP) group]. Offspring were analyzed at weaning for serum glucose, nonesterified fatty acids, triglyceride, and insulin. Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white adipose tissue using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: LLP and LP offspring were shorter, weighed less, had reduced serum insulin and nonesterified fatty acids, and had increased serum glucose, serum triglycerides, and hepatic triglycerides. Hepatic gene expression of acetyl-coenzyme A carboxylase and fatty acid synthase was increased 2-fold in LLP and LP offspring (p < 0.001). These changes were not seen in muscle or subcutaneous white adipose tissue. CPT-1 gene expression was unaltered in all tissues examined. DISCUSSION: Maternal protein energy malnutrition programs gene expression of lipogenic enzymes in the liver of weanling offspring in a manner favoring fat synthesis that may predispose these offspring to fat accumulation and insulin resistance later in life.

Acetyl-CoA Carboxylase↗
PubMed2003

A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men.

Fruit and vegetable consumption is inversely associated with coronary heart disease (CHD) risk. The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status. We assessed CHD risk by measuring the concentrations of homocysteine, lipids, lipoproteins, glucose and insulin. Men were recruited to participate in a randomized double-blind, crossover trial with 2 periods of 6 wk, separated by a 3-wk wash-out period. Supplementation with the encapsulated mixed extract (Juice Plus) was compared with physically similar placebo capsules. Thirty-two men (13 smokers, 19 nonsmokers) completed the study with a mean compliance of 88%. Compared with placebo, supplementation increased the concentrations of plasma beta-carotene (0.24 +/- 0.15 vs. 1.12 +/- 0.70 micro mol/L; mean +/- SD; P < 0.0001), retinol (1.87 +/- 0.33 vs. 2.00 +/- 0.43 micro mol/L; P < 0.05), alpha-tocopherol (16.8 +/- 7.3 vs. 19.3 +/- 6.8 micro mol/L; P < 0.01), ascorbic acid (72.1 +/- 19.4 vs. 84.1 +/- 13.5 micro mol/L; P < 0.002) and folic acid (24.5 +/- 10.0 vs. 44.9 +/- 16.9 nmol/L; P < 0.0001). Plasma homocysteine was reduced (8.2 +/- 1.5 vs. 7.6 +/- 1.1; P < 0.05) and inversely related (r = -0.40, P < 0.001) with serum folate concentrations. Plasma vitamin C was positively correlated with the resistance of LDL to oxidation (r = 0.26, P < 0.05) and the plasma ferric reducing/antioxidant power (FRAP) tended to be greater after supplementation than after the placebo period (1125.5 +/- 144.1 vs. 1180.3 +/- 158.1 micro mol/L; P < 0.065). Plasma glucose, insulin and lipid concentrations were unaffected. Responses of smokers and nonsmokers did not differ. In the absence of dietary modification, supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk.

Adult↗
PubMed2003

Hypertriglyceridemic waist as a screening tool for CVD risk in indigenous Australian women.

Research has demonstrated that the simultaneous determination of waist circumference and fasting plasma triglyceride (TG) concentrations can identify men characterized by a metabolic triad of unconventional risk variables: increased levels of fasting insulin, apolipoprotein (apo) B, and a predominance of small, dense, low density lipoprotein (LDL) particles. The aim of this study was to assess the efficacy of using "hypertriglyceridemic waist" to identify individuals at high risk of CVD in a sample of indigenous Australian women, for whom 2 of the 3 non-traditional risk factors were measured (apo B and insulin). Subjects (N=80) were divided into subgroups on the basis of waist girth and TG levels. The TG/HDL ratio increased in women with both elevated waist (above 95 cm) and TG levels (above 2.0 mmol/L), who were also characterized by lower HDL and elevated LDL concentrations. Although there was no trend toward an increase in apo B with increasing waist girth and TG levels, apo B concentration was highest among subgroups with elevated waist and TG levels. Fasting insulin levels were higher with increasing waist girth, but not with increasing TG levels. Utilizing hypertriglyceridemic waist as a marker of high plasma insulin and apo B can be an important factor in assessing cardiovascular risk in indigenous Australian women, despite an unexpected apo B distribution.

Anthropometry↗
PubMed2002

Association of the TNF-alpha -308 G/A promoter polymorphism with insulin resistance in obesity.

OBJECTIVE: Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)-alpha is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (-308 G/A) of the TNF-alpha gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population. RESEARCH METHODS AND PROCEDURES: Obese, non-diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance. RESULTS: The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high-density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r = -0.710; p < 0.001) occurred in subjects with the A allele only. DISCUSSION: The -308 G/A TNF-alpha gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.

Adult↗
PubMed2002

Obesity: epidemiology and possible prevention.

Obesity can be defined as the excessive accumulation of fat in adipose tissue, to the extent that health may be impaired. The most widely used measures of total and abdominal adiposity are the body mass index and waist circumference. Obesity is now a global public health problem, with about 315 million people world-wide estimated to fall into the WHO-defined obesity categories with a body mass index (BMI) of 30 or above. The primary causes of the rapid global rise in obesity rates lie in the profound environmental and societal changes now affecting large parts of the world and creating societies in which physical activity is low and the availability of high-fat, energy-dense foods has increased. Strategies aimed at preventing weight gain and obesity have not been successful to date but are likely to be more cost effective, and to have a greater positive impact on long-term control of body weight than treating obesity once it has developed.

Adult↗
PubMedDate not supplied

Snowballing obesity: Australians will get run over if they just sit there.

Overweight and obesity are very common in Australian adults (56%) and children (27%). Rates of overweight and obesity are snowballing and will place greater burdens on health services for the treatment and care of chronic diseases. Prevention is urgently required from health, social and economic perspectives, but the response to date has been inadequate. A long-term, sustained action plan starting with a focus on young people is needed. This should particularly address the "obesogenic" environments causing the epidemic. Although whole-of-government action is required, support from and involvement by parents, carers, community leaders, healthcare professionals, teachers, childcare workers, urban planners, recreation managers, food manufacturers, employers, advertisers, and communicators is essential. The health sector should take the lead, but success will only come from concerted and integrated action across the whole of society. There are now signs of political commitment to addressing overweight and obesity. Doctors should get behind this and help mobilise community support.

Adult↗