Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance

OBJECTIVE: To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance.

DESIGN: Cross-sectional studies in 27 non-diabetic human subjects and in Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes.

MEASUREMENTS: Expression of CAPN3 in skeletal muscle was measured using Taqman fluorogenic PCR. In the human subjects, body composition was assessed by DEXA and insulin sensitivity was measured by euglycemic-hyperinsulinemic clamp. In Psammomys obesus, body composition was determined by carcass analysis, and substrate oxidation rates, physical activity and energy expenditure were measured by whole-body indirect calorimetry.

RESULTS: In human subjects, calpain 3 gene expression was negatively correlated with total (P=0.022) and central abdominal fat mass (P=0.034), and with blood glucose concentration in non-obese subjects (P=0.017). In Psammomys obesus, calpain 3 gene expression was negatively correlated with circulating glucose (P=0.013) and insulin (P=0.034), and with body fat mass (P=0.049). Indirect calorimetry revealed associations between calpain 3 gene expression and carbohydrate oxidation (P=0.009) and energy expenditure (P=0.013).

CONCLUSION/INTERPRETATION: Lower levels of expression of calpain 3 in skeletal muscle were associated with reduced carbohydrate oxidation and elevated circulating glucose and insulin concentrations, and also with increased body fat and in particular abdominal fat. Therefore, reduced expression of calpain 3 in both humans and Psammomys obesus was associated with phenotypes related to obesity and insulin resistance.

Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus

It has been reported previously that leptin may be involved in nicotine's ability to reduce body weight. Our aim was to investigate whether the anorexic action of nicotine is related to the actions of leptin by utilizing lean leptin-sensitive and obese leptin-resistant Psammomys obesus. Lean and obese P. obesus were assigned to receive nicotine sulphate at 6, 9 or 12 mg/day or saline (control) for 9 days (n = 6-10 in each group), administered using mini-osmotic pumps. Food intake, body weight, plasma leptin concentrations, plasma insulin and blood glucose were measured at baseline and throughout the study period. Nicotine treatment reduced food intake by up to 40% in lean and obese P. obesus. Plasma leptin levels fell significantly only in lean nicotine-treated animals, whereas no changes were observed in obese nicotine-treated animals. However, both lean and obese nicotine-treated animals had similar reductions in body weight. Our results show that nicotine has dramatic effects on food intake and body weight, however, these changes appear to be independent of the leptin signalling pathway.

Elevation in tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells

Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

Patterns and demographic predictors of 5-year weight change in a multi-ethnic cohort of men and women in Australia

Objective: This study investigated 5-year trends in body weight, overweight and obesity and their association with sociodemographic variables in a large, multi-ethnic community sample of Australian adults.  Design: This prospective population study used baseline and 5-year follow-up data from participants in the Melbourne Collaborative Cohort Study (MCCS). Setting: Population study in Melbourne, Australia. Subjects: In total, 12 125 men and 17 674 women aged 35–69 years at baseline. Results: Mean 5-year weight change in this sample was +1.58 (standard deviation (SD) 4.82) kg for men and +2.42 (SD 5.17) kg for women. Younger (35–44 years) men and, in particular, women gained more weight than older adults and were at highest risk of major weight gain ($5 kg) and becoming overweight. Risk of major weight gain and associations between demographic variables and weight change did not vary greatly by ethnicity. Education level showed complex associations with weight outcomes that differed by sex and ethnicity. Multivariate analyses showed that, among men, higher initial body weight was associated with decreased likelihood of major weight gain, whereas among women, those initially overweight or obese were about 20% more likely to experience major weight gain than underweight or healthy weight women. Conclusions: Findings of widespread weight gain across this entire population sample, and particularly among younger women and women who were already overweight, are a cause for alarm. The prevention of weight gain and obesity across the entire population should be an urgent public health priority. Young-to-mid adulthood appears to be a critical time to intervene to prevent future weight gain.

Beacon interacts with cdc2/cdc28-like kinases

Previously we found elevated beacon gene expression in the hypothalamus of obese Psammomys obesus. Beacon administration into the lateral ventricle of P. obesus stimulated food intake and body weight gain. In the current study we used yeast two-hybrid technology to screen for proteins in the human brain that interact with beacon. CLK4, an isoform of cdc2/cdc28-like kinase family of proteins, was identified as a strong interacting partner for beacon. Using active recombinant proteins and a surface plasmon resonance based detection technique, we demonstrated that the three members of this subfamily of kinases (CLK1, 2, and 4) all interact with beacon. Based on the known sequence and functional properties of beacon and CLKs, we speculate that beacon could either modulate the function of key regulatory molecules such as PTP1B or control the expression patterns of specific genes involved in the central regulation of energy metabolism.

Identification of hypothalamic genes implicated in the development of obesity in Psammomys obesus using differential display PCR

The hypothalamus is a key central controller of energy homeostasis and is the source and/or site of action of many neuropeptides involved in this process. The aim of this study was to isolate hypothalamic genes differentially expressed between lean and obese Psammomys obesus, a polygenic animal model of obesity and type 2 diabetes. Differential display PCR was used to compare hypothalamic gene expression profiles of lean and healthy, obese and hyperinsulinemic, and obese, diabetic P. obesus in both the fed and fasted states. We conducted differential display with 180 separate primer combinations to amplify approximately 9000 expressed transcripts. Sixty differentially expressed bands were excised. Taqman PCR was performed on 36 of these transcripts to confirm differential gene expression in a larger sample population. Of these 36 transcripts, 9 showed homology to known genes, and 27 were considered to be novel sequences. Gene expression profiles for two of these genes are presented here. In conclusion, differential display PCR was successfully used to isolate several transcripts that may be involved in the central regulation of energy balance. We are currently conducting numerous studies to further investigate the role of these genes in the development of obesity in P. obesus.

Diet, nutrition and the prevention of excess weight gain and obesity

Objective: To review the evidence on the diet and nutrition causes of obesity and to recommend strategies to reduce obesity prevalence.
Design: The evidence for potential aetiological factors and strategies to reduce obesity prevalence was reviewed, and recommendations for public health action, population nutrition goals and further research were made.
Results: Protective factors against obesity were considered to be: regular physical activity (convincing); a high intake of dietary non-starch polysaccharides (NSP)/fibre (convincing); supportive home and school environments for children (probable); and breastfeeding (probable). Risk factors for obesity were considered to be sedentary lifestyles (convincing); a high intake of energy-dense, micronutrient-poor foods (convincing); heavy marketing of energy-dense foods and fast food outlets (probable); sugar-sweetened soft drinks and fruit juices (probable); adverse social and economic conditions—developed countries, especially in women (probable).
A broad range of strategies were recommended to reduce obesity prevalence including: influencing the food supply to make healthy choices easier; reducing the marketing of energy dense foods and beverages to children; influencing urban environments and transport systems to promote physical activity; developing community-wide programmes in multiple settings; increased communications about healthy eating and physical activity; and improved health services to promote breastfeeding and manage currently overweight or obese people.
Conclusions: The increasing prevalence of obesity is a major health threat in both low- and high income countries. Comprehensive programmes will be needed to turn the epidemic around.

Longitudinal relationships among overweight, life satisfaction, and aspirations in young women

Objective: This study investigated associations of overweight status and changes in overweight status over time with life satisfaction and future aspirations among a community sample of young women.
Research Methods and Procedures: A total of 7865 young women, initially 18 to 23 years of age, completed two surveys that were 4 years apart. These women provided data on their future life aspirations in the areas of further education, work/career, marital status, and children, as well as their satisfaction with achievements to date in a number of life domains. Women reported their height and weight and their sociodemographic characteristics, including current socioeconomic status (occupation).
Results: Young women's aspirations were cross-sectionally related to BMI category, such that obese women were less likely to aspire to further education, although this relationship seemed explained largely by current occupation. Even after adjusting for current occupation, young women who were obese were more dissatisfied with work/career/study, family relationships, partner relationships, and social activities. Weight status was also longitudinally associated with aspirations and life satisfaction. Women who were overweight or obese at both surveys were more likely than other women to aspire to "other" types of employment (including self-employed and unpaid work in the home) as opposed to full-time employment. They were also less likely to be satisfied with study or partner relationships. Women who resolved their overweight/obesity status were more likely to aspire to being childless than other women.
Discussion: These results suggest that being overweight/obese may have a lasting effect on young women's life satisfaction and their future life aspirations.

Effect of migration on food habits of Somali women living as refugees in Australia

This study aimed to assess the dietary changes that occur for migrants moving from a low-income to a high-income country. The sample included 45 females who had migrated to Australia from Somalia within the past 5years (1996-2001). The data for the study was derived from structured interviews conducted by a bilingual interviewer and anthropometry. Usual dietary intake and frequency of consumption of 54 foods were determined both for Australia (current home) and for Somalia (previous home). In Australia, subjects maintained the structure of the diet from their country of birth. They did increase their consumption of some processed food, such as instant noodles, crisps, and pizza. However, there was little evidence that the subjects adopted ready or partially prepared meals or takeaway meals. A significant addition to the diet in Australia was the use of breakfast cereals. Significant substitutions were of ready-baked bread for traditional bread and lamb for camel meat. The mean BMI of the sample was 27.4kg/m². Sixty percent of the sample were overweight or obese (BMI>25). Some of the dietary changes observed may be consistent with increased energy intake and altered nutrient density. Given the association between transition to a high-income diet and obesity, it is important that migrants are encouraged to retain the best of their traditional diet while adopting healthy foods from host country.

An investigation into the incidence of obesity and underweight among adults with an intellectual disability in an Australian sample

Reports suggest that 7% to 18% of Australian adults are obese and a further 16% to 55% are overweight. Studies from other countries have indicated that obesity among people with an intellectual disability may be at least, or even more, prevalent. Prevalence rates range from 28% to 59%. The aim of the current study was to investigate the weight distribution of an Australian sample of people with an intellectual disability using Body Mass Index (BMI) to classify males and females, and Kelly and Rimmer's (1987) Percentage of Body Fat (PBF) formula to also classify males. Forty-one females and 52 males with a mild to severe intellectual disability were assessed. The correlation between BMI and PBF for males was r=.89. BMI classifications revealed a higher percentage of females as overweight (41.4%) and obese (36.6%) compared to overweight males (30.8%) and obese males (30.8%). There were more underweight males (7.6%) than females (4.9%). There was no relationship between living environment and weight classifications on the BMI. The PBF formula indicated that 73% of the males were classified as obese. The possibility of misclassification using the BMI and the need for weight interventions are discussed.

Perceptions of local neighbourhood environments and their relationship to childhood overweight and obesity

OBJECTIVES: To examine associations between parent and child perceptions of the local neighbourhood and overweight/obesity among children aged 5–6 and 10–12 y. DESIGN: Cross-sectional survey. SUBJECTS: In total, 291 families of 5–6-y-old and 919 families of 10–12-y-old children. MEASURES: Parent's perceptions of local neighbourhood and perceived child access to eight local destinations within walking distance of home; 10–12-y-old children's perception of local neighbourhood; socio-demographic characteristics (survey). Children's height and weight (measured). RESULTS: No perceptions of the local neighbourhood were associated with weight status among 5–6-y-old children. Among 10–12-y-old children, those whose parents agreed that there was heavy traffic in their local streets were more likely to be overweight or obese (OR=1.4, 95% CI=1.0–1.8), and those whose parents agreed that road safety was a concern were more likely to be obese (OR=3.9, 95% CI=1.0–15.2), compared to those whose parents disagreed with these statements. CONCLUSIONS: This study suggests that parental perceptions of heavy traffic on local streets and concern about road safety may be indirect influences on overweight and obesity among 10–12-y-old children. Future work should also consider perceptions of the neighbourhood related to food choice.

Trends in children`s physical activity and weight status in high and low socio-economic status areas of Melbourne, Victoria, 1985-2001

Objective:
To examine trends in active transport to and from school, in school sport and physical education (PE), and in weight status among children from high and low socio-economic status (SES) areas in Melbourne, Victoria, between 1985 and 2001.

Methods:
Cross-sectional survey data and measured height and weight from 1985 (n=557) and 2001 (n=926) were compared for children aged between 9–13 years within high and low SES areas.

Results:
From 1985 to 2001, the frequency of walking to or from school declined (4.38±4.3 vs. 3.61 ± 3.8 trips/wk, p<0.001), cycling to or from school also declined (1.22±2.9 vs. 0.36±1.5 trips/wk, p<0.001), and the frequency of PE lessons declined (1.64±1.1 vs. 1.18±0.9 lessons/wk, p<0.001). However, the frequency of school sport increased (0.9±1.22 vs. 1.24±0.8 sessions/wk, p<0.001). In 1985, 11.7% of children were overweight or obese compared with 28.7% in 2001 (p<0.001). Apart from walking to school and school sport, there were greater relative declines in cycling to school and PE, and increases in overweight and obesity among children attending schools in low SES areas compared with those attending schools in high SES areas.

Conclusions:
Declines in active school transport and PE have occurred at the same time as increases in overweight and obesity among Australian children.

Implications:
Promoting active school transport and maintaining school sport and PE should be important public health priorities in Australia. Current inequities in school sport and PE and in prevalence of overweight and obesity by area-level SES also need to be addressed.

Fat and the law: who should take the blame?

The incidence of obesity in both adults and children is rising at a rapid rate in most developed countries, including in Australia. Some obese people are seeking to place the blame for their condition on the fast-food industry, as demonstrated by the recent litigation in the United States brought by two obese plaintiffs against McDonald's. This litigation was unsuccessful, and on existing Australian negligence principles any similar litigation commenced here is likely to suffer the same fate. Principles of personal responsibility, autonomy and free will should prevail to deny a negligence claim. The risk of obesity and concomitant health problems from eating fast food to excess is an obvious risk which the plaintiff should not have ignored and which he or she has voluntarily assumed. It is for the Australian Government, not the courts, to regulate the behaviour of the fast-food industry. The government should take action by requiring all major fast-food chains to label their products with nutritional information, and by imposing restrictions on the advertising of food to children.

Obesity and the right to sue: would you like fries with that?

There is little chance that obese customers in Australia would fare any better in a claim against fast food companies than their counterparts in the US.

Socio-economic factors in obesity: a case of slim chance in a fat world?

The global obesity pandemic has been well-documented and widely discussed by the public, the media, health officials, the food industry and academic researchers. While the problem is widely recognised, the potential solutions are far less clear. There is only limited evidence to guide decisions as to how best to manage obesity in individuals and in populations. While widely viewed as a clinical and public health problem in developed countries, it is now clear that many developing countries also have to grapple with this problem or face the crippling healthcare costs resulting from obesity-related morbidity. There is also abundant evidence that obesity is socio-economically distributed. In developed countries persons of lower socio-economic position are more likely to be affected, while in developing countries, it is often those of higher socio-economic position who are overweight or obese. The aim of this paper is to briefly review the evidence that links socio-economic position and obesity, to discuss what is known about underlying mechanisms, and to consider the role of social, physical, policy and cultural environments in explaining the relationships between socio-economic position and obesity. We introduce the concept of ‘resilience’ as a potential theoretical construct to guide research efforts aimed at understanding how some socio-economically disadvantaged individuals manage to avoid obesity. We conclude by considering an agenda to guide future research and programs focused on understanding and reducing obesity among those of low socio-economic position.