Television viewing habits associated with obesity risk factors: a survey of Melbourne schoolchildren.

Objectives: To examine whether children’s television viewing may be a useful indicator of risk of obesity-promoting versus healthy eating behaviours, low-level physical activity (PA) and overweight or obesity among children of primary school entry and exit ages. Design: Cross-sectional study, stratified by area-level socioeconomic status. Participants and setting: 1560 children (613 aged 5–6 years [50% boys], and 947 aged 10–12 years [46% boys]) from 24 primary schools in Melbourne, Australia, randomly selected proportionate to school size between 1 November 2002 and 30 December 2003 . Main outcome measures: Parents’ reports of the time their child spends watching television, their participation in organised physical activities (PA), and their food intake; each child’s measured height and weight and their PA levels as assessed by accelerometry for one week. Results: After adjusting for the age and sex of child, the parents’ level of education, clustering by school, and all other health behaviour variables, children who watched television for > 2 h/day were significantly more likely than children who watched television for ≤ 2 h/day to: to have one or more serves/day of high energy drinks (adjusted odds ratio [AOR], 2.31; 95% CI, 1.61–3.32), and to have one or more serves/day of savoury snacks (AOR, 1.50; 95% CI, 1.04–2.17). They were also less likely to have two or more serves/day of fruit (AOR, 0.58; 95% CI, 0.46–0.74), or to participate in any organised PA (AOR, 0.52; 95% CI, 0.34–0.80). Conclusions: Health practitioners in the primary care setting may find that asking whether a child watches television for more than 2 hours daily can be a useful indicator of a child’s risk of poor diet and low physical activity level.

Genetic albation of the c-Cbl ubiquitin ligase domain results in increased energy expenditure and improved insulin action

Casitas b-lineage lymphoma (c-Cbl) is a multiadaptor protein with E3-ubiquitin ligase activity residing within its RING finger domain. We have previously reported that c-Cbl–deficient mice exhibit elevated energy expenditure, reduced adiposity, and improved insulin action. In this study, we examined mice expressing c-Cbl protein with a loss-of-function mutation within the RING finger domain (c-Cbl^A/– mice). Compared with control animals, c-Cbl^A/– mice display a phenotype that includes reduced adiposity, despite greater food intake; reduced circulating insulin, leptin, and triglyceride levels; and improved glucose tolerance. c-Cbl^A/– mice also display elevated oxygen consumption (13%) and are protected against high-fat diet–induced obesity and insulin resistance. Unlike c-Cbl^A/– mice, mice expressing a mutant c-Cbl with the phosphatidylinositol (PI) 3-kinase binding domain ablated (c-Cbl^F/F mice) exhibited an insulin sensitivity, body composition, and energy expenditure similar to that of wild-type animals. These results indicate that c-Cbl ubiquitin ligase activity, but not c-Cbl–dependent activation of PI 3-kinase, plays a key role in the regulation of whole-body energy metabolism.

Association of genetic vatiation within UBL5 with phenotypes of metabolic syndrome

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action

Casitas b-lineage lymphoma (c-Cbl) is an E3 ubiquitin ligase that has an important role in regulating the degradation of cell surface receptors. In the present study we have examined the role of c-Cbl in whole-body energy homeostasis. c-Cb^-/- mice exhibited a profound increase in whole-body energy expenditure as determined by increased core temperature and whole-body oxygen consumption. As a consequence, these mice displayed a decrease in adiposity, primarily due to a reduction in cell size despite an increase in food intake. These changes were accompanied by a significant
increase in activity (2- to 3-fold). In addition, cc-Cb-/- mice displayed a marked improvement in whole-body insulin action, primarily due to changes in muscle metabolism. We observed increased protein levels of the insulin receptor (4-fold) and uncoupling protein-3 (2-fold) in skeletal muscle and a significant increase in the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. These fmdings suggest that c-Cbl plays an integral role in whole-body fuel homeostasis by regulating whole-body energy expenditure and insulin action.

Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

Relationship between stress, eating behavior and obesity

Stress is thought to influence human eating behavior and has been examined in animal and human studies. Our understanding of the stress-eating relation is confounded by limitations inherent in the study designs; however, we can make some tentative conclusions that support the notion that stress can influence eating patterns in humans. Stress appears to alter overall food intake in two ways, resulting in under- or overeating, which may be influenced by stressor severity. Chronic life stress seems to be associated with a greater preference for energy- and nutrient-dense foods, namely those that are high in sugar and fat. Evidence from longitudinal studies suggests that chronic life stress may be causally linked to weight gain, with a greater effect seen in men. Stress-induced eating may be one factor contributing to the development of obesity. Future studies that measure biological markers of stress will assist our understanding of the physiologic mechanism underlying the stress-eating relation and how stress might be linked to neurotransmitters and hormones that control appetite.

Angiotensin converting enzyme inhibition from birth reduces body weight and body fat in Sprague-Dawley rats

In vitro studies have demonstrated that angiotensin II (ANG II) induces adipocyte hyperplasia and hypertrophy. The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibition on body weight, adiposity and blood pressure in Sprague–Dawley rats. From birth half of the animals (n = 15) were given water to drink, while the remainder were administered perindopril in their drinking water (2 mg/kg/day). Food intake, water intake and body weight were measured weekly. Blood pressure was measured by tail cuff plethysmography at 11-weeks. Body fat content and distribution were assessed using dual energy X-ray absorptiometry and Magnetic Resonance Imaging at 12 weeks. Animals administered with perindopril had a body fat proportion that was half that of controls. This was consistent with, but disproportionately greater than the observed differences in food intake and body weight. Perindopril treatment completely removed hypertension. We conclude that the chronic inhibition of ANG II synthesis from birth specifically reduces the development of adiposity in the rat.

Socio-demographic inequalities in the diets of mid-aged Australian women

Objectives: This study reports on the distributions of food and nutrient intakes by socio-demographic factors for a large population sample of mid-aged Australian women participating in the Australian Longitudinal Study on Women's Health.
Design: This cross-sectional population-based study used the Cancer Council of Victoria food frequency questionnaires to derive estimates of food and nutrient intakes.
Setting: Nationwide community-based survey.
Subjects: A total of 10561 women aged 50-55 y, at the time of the survey in 2001.
Results: Analysis showed favourable patterns of food intake, with frequent consumption of many foods that are promoted as components of a healthy diet (eg, fresh fruit, leafy green and other vegetables, bread, cereals, milk and meat). Intakes of both foods and nutrients varied significantly across socio-demographic groups, with unmarried women, and women in 'labouring' occupations (eg, cleaner, factory worker, kitchenhand) having poorer nutrient intake.
Conclusions: Although many mid-aged women in this sample had generally healthful diets, women in certain socio-demographic groups (particularly unmarried women and those in labouring occupations) had nutrient intakes of concern. As well as helping to address the dearth of current data on dietary intakes in the Australian population, the results highlight the need for continued targeted public health strategies aimed at improving diet of women from the various socio-economic backgrounds.

GAD2 on chromosome 10p12 is a candidate gene for human obesity

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11–12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of γ-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681–0.972], p = 0.0049) and an at-risk SNP (−243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053–1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (χ2 = 7.637, p = 0.02). In the murine insulinoma cell line βTC3, the G at-risk allele of SNP −243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The −243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic β cells, we analyzed GAD65 antibody level as a marker of β-cell activity and of insulin secretion. In the control group, −243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of β-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.

Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance

To identify genes involved in the central regulation of energy balance, we compared hypothalamic mRNA from lean and obese Psammomys obesus, a polygenic model of obesity, using differential display PCR. One mRNA transcript was observed to be elevated in obese, and obese diabetic, P. obesus compared with lean animals and was subsequently found to be increased 4-fold in the hypothalamus of lethal yellow agouti (Ay/a) mice, a murine model of obesity and diabetes. Intracerebroventricular infusion of antisense oligonucleotide targeted to this transcript selectively suppressed its hypothalamic mRNA levels and resulted in loss of body weight in both P. obesus and Sprague Dawley rats. Reductions in body weight were mediated by profoundly reduced food intake without a concomitant reduction in metabolic rate. Yeast two-hybrid screening, and confirmation in mammalian cells by bioluminescence resonance energy transfer analysis, demonstrated that the protein it encodes interacts with endophilins, mediators of synaptic vesicle recycling and receptor endocytosis in the brain. We therefore named this transcript Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes a large proline-rich protein that is expressed predominantly in the brain and is highly conserved between species. Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis.

Television, computer use and body mass index in Australian primary school children

Objective: To investigate relationships between children's body mass index (BMI) and parent reports of children's television and video game/computer habits, controlling for other potential risk factors for paediatric obesity.

Methods: Child BMI was calculated from measured height and weight collected in 1997 as part of a large, representative, cross-sectional study of children in Victoria, Australia. Parents reported the amount of time children watched television and used video games/computers, children's eating and activity habits, parental BMI and sociodemographic details.

Results: A total of 2862 children aged 5−13 years participated. Child mean BMI z-score was significantly related to television (F = 10.2₃, P < 0.001) but not video game/computer time (F = 2.2₃, P = 0.09), but accounted for only 1 and 0.2% of total BMI variance, respectively. When parental BMI, parental education, number of siblings, food intake, organized exercise and general activity level were included, television ceased to be independently significantly related to child BMI. Using adjusted logistic regression, the odds of being overweight and obese generally increased with increasing television viewing. No relationship was found for video game/computer use.
Conclusions: A small proportion of variance in child BMI was related to television, but not video game/computer time. This was far outweighed by the influence of other variables. Causal pathways are likely to be complex and interrelated.

Does perinatal ω-3 polyunsaturated fatty acid deficiency increase appetite signaling?

Objective: To investigate the effect of maternal dietary ω-3 polyunsaturated fatty acid (PUFA) deficiency and repletion on food appetite signaling.
Research Methods and Procedures: Sprague-Dawley rat dams were maintained on diets either supplemented with (CON) or deficient in (DEF) ω-3 PUFA. All offspring were raised on the maternal diet until weaning. After weaning, two groups remained on the respective maternal diet (CON and DEF groups), whereas a third group, born of dams fed the DEF diet, were switched to the CON diet (REC). Experiments on food intake began when the male rats reached 16 weeks of age. Food intake was stimulated either by a period of food restriction, by blocking glucose utilization (by 2-deoxyglucose injection), or by blocking β-oxidation of fatty acids (by β-mercaptoacetate injection).
Results: DEF animals consumed more than CON animals in response to all stimuli, with the greatest difference (1.9-fold) demonstrated following administration of 2-deoxyglucose. REC animals also consumed more than CON animals in response to food restriction and 2-deoxyglucose but not to β-mercaptoacetate.
Discussion: These findings indicate that supply of ω-3 PUFA, particularly during the perinatal period, plays a role in the normal development of mechanisms controlling food intake, especially glucoprivic (i.e. reduced glucose availability) appetite signaling. Dietary repletion of ω-3 PUFA from 3 weeks of age restored intake responses to fatty acid metabolite signaling but did not reverse those in response to food restriction or glucoprivic stimuli.

Is the perception of time pressure a barrier to healthy eating and physical activity among women?

Objectives To describe the proportion of women reporting time is a barrier to healthy eating and physical activity, the characteristics of these women and the perceived causes of time pressure, and to examine associations between perceptions of time as a barrier and consumption of fruit, vegetables and fast food, and physical activity.
Design A cross-sectional survey of food intake, physical activity and perceived causes of time pressure.
Setting A randomly selected community sample.
Subjects A sample of 1580 women self-reported their food intake and their perceptions of the causes of time pressure in relation to healthy eating. An additional 1521 women self-reported their leisure-time physical activity and their perceptions of the causes of time pressure in relation to physical activity.
Results Time pressure was reported as a barrier to healthy eating by 41 % of the women and as a barrier to physical activity by 73 %. Those who reported time pressure as a barrier to healthy eating were significantly less likely to meet fruit, vegetable and physical activity recommendations, and more likely to eat fast food more frequently.
Conclusions Women reporting time pressure as a barrier to healthy eating and physical activity are less likely to meet recommendations than are women who do not see time pressure as a barrier. Further research is required to understand the perception of time pressure issues among women and devise strategies to improve women’s food and physical activity behaviours.

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

Objective: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. Design: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg⁻¹ per day) in drinking water for 26 days.Subjects: In total, 16 male Sprague–Dawley rats aged 10 weeks at the start of the study. Measurements: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. Results: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4±5.0 g vs 73.0±4.0 g; P<0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0±5.2 g vs 44.4±4.2 g; P<0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (P<0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64±0.56 ng ml⁻¹) compared to the untreated group (8.27±1.03 ng ml⁻¹; P<0.001). In contrast, there were no differences in lean or bone mass between the two groups.Conclusion: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups

Outcomes of a group-randomized trial to prevent excess weight gain, reduce screen behaviours and promote physical activity in 10-year-old children : switch-play

Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain, reduce time spent in screen behaviours, promote participation in and enjoyment of physical activity (PA), and improve fundamental movement skills among children.

Participants : In 2002, 311 children (78% response; 49% boys), average age 10 years 8 months, were recruited from three government schools in low socioeconomic areas of Melbourne, Australia.

Design : Group-randomized controlled trial. Children were randomized by class to one of the four conditions: a behavioural modification group (BM; n=66); a fundamental movement skills group (FMS; n=74); a combined BM/FMS group (BM/FMS; n=93); and a control (usual curriculum) group (n=62). Data were collected at baseline, post intervention, 6- and 12-month follow-up periods.

Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up. After adjusting for food intake and PA, there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls (-1.88 kg m-2, P<0.01), which was maintained at 6- and 12-month follow-up periods (-1.53 kg m-2, P<0.05). Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention (adjusted odds ratio (AOR)=0.36, P<0.05); also maintained at 12-month follow-up (AOR=0.38, P<0.05). Compared with controls, FMS group children recorded higher levels and greater enjoyment of PA; and BM children recorded higher levels of PA and TV viewing across all four time points. Gender moderated the intervention effects for participation in and enjoyment of PA, and fundamental movement skills.

Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA. Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required.