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.

Increasing central adiposity: the Nepean longitudinal study of young people aged 7-8 to 12-13y

BACKGROUND: Estimates of the prevalence of overweight and obesity in young people are typically based on body mass index (BMI). However, BMI may not indicate the level of central adiposity. Waist circumference has therefore been recommended to identify young people at risk of morbidity associated with central adiposity.

OBJECTIVE: To investigate (a) change in total and central adiposity between 7–8 and 12–13 y (b) agreement between classifying young people as overweight or obese based on total adiposity and central adiposity, and (c) risk factors associated with the development of total and central adiposity.

DESIGN: Anthropometric measurements were taken on 342 children in 1996/97 and 5 y later. Risk factors examined included birth weight, physical activity, TV viewing, pubertal status, parental adiposity, diet and socio-economic status.

RESULTS: Between 7–8 and 12–13 y indices of central adiposity increased more than total adiposity; waist circumference z-score increased by (means.d.) 0.740.92 and BMI z-score increased by 0.180.67. At 12–13 y there was moderate agreement between the two measures of adiposity (weighted kappa=0.64). However, waist circumference identified a greater number of young people as overweight or obese compared to BMI (41.2 vs 29.3%, P<0.001). Adiposity status at 7–8 y, maternal obesity, and pubertal stage were the strongest predictors of BMI status at 12–13 y. Risk factors associated with increased central adiposity were similar.

CONCLUSIONS: Overweight and obesity, as measured by waist circumference, is a bigger problem than is currently assessed by BMI. Targeting known risk factors for total adiposity may be an appropriate strategy for preventing increased central adiposity.

Discordance of international adiposity classifications in Australian boys and girls - The LOOK study

Background: Various charts based on body mass index (BMI) and per cent body fat (%BF) are used to classify childhood body composition but outcomes may vary.

Aim: The study investigated variation in incidences of childhood obesity as depicted by four classification charts.

Subjects and methods: BMI and DXA-derived %BF were assessed in 741 children. Incidences of overweight and obesity were compared between two BMI charts and two bioelectrical impedance (BIA)-based %BF charts.

Results: The International Obesity Task Force (IOTF)-adopted BMI chart designated 21%, 6% (boys), and 26%, 9% (girls) as overweight and obese, respectively. Corresponding figures using the USA CDC BMI chart were 27%, 11% (boys) and 27%, 12% (girls). Using a USA-derived %BF chart incidences were 17%, 2% (boys) and 21%, 8% (girls) and using a UK-derived %BF chart 51%, 24% (boys) and 53%, 36% (girls). Sensitivity of BMI varied according to the %BF reference chart.

Conclusions: In contrast to the BMI-based charts, there were considerable variations in depicted incidences of obesity between the %BF-based charts. These discordances were considered to result from previously reported variation within and between BIA and DXA %BF assessments underlying the charts. The present study highlights the need for valid, reliable, unchanging BIA and DXA procedures.

Adiposity and tendinopathy

Purpose. Tendon injuries (tendinopathy) are prevalent across the population, affecting active and inactive individuals and manual workers. The aetiology of tendinopathy is not known. However, extrinsic factors such as load are known to affect the prevalence. More recently, intrinsic factors have been shown to also affect tendons; genes, biomechanics, and strength have been shown to influence tendon disease. One intrinsic factor that appears to have an association with tendinopathy is body composition; more specifically central adiposity. Several studies have reported this association, and several studies have found the association when reporting other aspects of tendinopathy.

Method. This paper will detail what is known about the association between tendinopathy and body composition, examine the strength of the association by evaluating studies in the area and speculate on potential mechanisms for the association.

Results. The association between tendon health and adiposity, especially central adiposity, warrants further investigation.

Conclusion. There may be an interaction between adiposity and tendon pathology. Adiposity may be a key intrinsic risk factor that is translated into tendon disease in the presence of additional intrinsic (e.g., diabetes) and extrinsic factors (e.g., load).

Responses of the hypothalamopituitary adrenal axis and the sympathoadrenal system to isolation/restraint stress in sheep of different adiposity

There is evidence that levels of adipose tissue can influence responses of the hypothalamopituitary-adrenal (HPA) axis to stress in humans and rats but this has not been explored in sheep. Also, little is known about the sympathoadrenal responses to stress in individuals with relatively different levels of adipose tissue. We tested the hypothesis that the stress-induced activation of the HPA axis and sympathoadrenal system is lower in ovariectomized ewes with low levels of body fat (lean) than ovariectomized ewes with high levels of body fat (fat). Ewes underwent dietary manipulation for 3 months to yield a group of lean ewes (n = 7) with a mean (±SEM) live weight of 39.1 ± 0.9 kg and body fat of 8.9 ± 0.6% and fat ewes (n = 7) with a mean (±SEM) live weight of 69.0 ± 1.8 kg and body fat of 31.7 ± 3.4%. Fat ewes also had higher circulating concentrations of leptin than lean ewes. Blood samples were collected every 15 min over 8 h when no stress was imposed (control day) and on a separate day when 4 h of isolation/restraint was imposed after 4 h of pretreatment sampling (stress day). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, epinephrine and norepinephrine did not change significantly over the control day and did not differ between lean and fat ewes. Stress did not affect plasma leptin levels. All stress hormones increased significantly during isolation/restraint stress. The ACTH, cortisol and epinephrine responses were greater in fat ewes than lean ewes but norepinephrine responses were similar. Our results suggest that relative levels of adipose tissue influence the stress-induced activity of the hypothalamopituitary-adrenal axis and some aspects of the sympathoadrenal system with fat animals having higher responses than lean animals.

Is adiposity an under-recognized risk factor for tendinopathy? A systematic review

Objective : Tendon injuries have been reported to occur more frequently in individuals with increased adiposity. Treatment also appears to have poorer outcomes among these individuals. Our objective was to examine the extent and consistency of associations between adiposity and tendinopathy.

Methods : A systematic review of observational studies was conducted. Eight electronic databases were searched (Allied and Complementary Medicine, Biological Abstracts, CINAHL, Current Contents, EMBase, Medline, SPORTDiscus, and Web of Science) and citation tracking was performed on included reports. Studies were included if they compared adiposity between subjects with and without tendon injury or examined adiposity as a predictor of conservative treatment success.

Results : Four longitudinal cohorts, 14 cross-sectional studies, 8 case-control studies, and 2 interventional studies (28 in total) met the inclusion criteria, providing a total of 19,949 individuals. Forty-two subpopulations were identified, 18 of which showed elevated adiposity to be associated with tendon injury (43%). Sensitivity analyses indicated a clustering of positive findings among studies that included clinical patients (81% positive) and among case-control studies (77% positive).

Conclusion : Elevated adiposity is frequently associated with tendon injury. Published reports suggest that elevated adiposity is a risk factor for tendon injury, although this association appears to vary depending on aspects of study design and measurement. Adiposity is of particular interest in tendon research because, unlike a number of other reported risk factors for tendon injury, it is somewhat preventable and modifiable. Further research is required to determine if reducing adiposity will reduce the risk of tendon injury or improve the results of treatment.

Adiposity and its metabolic consequences contribute to Achilles tendinopathy

Pain in the Achilles tendon commonly affects active individuals but is also seen in sedentary people. This thesis shows that the accumulation of excess body fat, abnormal blood lipids and glucose metabolism were associated with Achilles tendinopathy. Targeting these lifestyle factors may improve treatment outcomes for tendon injury.

Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children

Background/Aim: The study investigated the relationship between indices of adiposity measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) in pre-pubertal children.

Subjects and methods: DXA-derived per cent body fat (%BF) was measured in 284 boys and 288 girls, aged 7–10 years. Cross-sections of the forearm (n=427) and lower leg (n=560) were obtained by pQCT to measure total cross-sectional area of the limb (Total CSA), Muscle CSA, Fat CSA, %Fat CSA (Fat CSA/Total CSA×100) and muscle density.

Results: Peripheral QCT-derived %Fat CSA in the forearm and lower leg correlated strongly with DXA-derived %BF (r=0.83–0.89, p<0.01) in both boys and girls. However, forearm and lower leg %Fat CSA were higher than whole body %BF by 5% and 10%, respectively. A better prediction of whole-body %BF was achieved by including %Fat CSA, muscle density and height into a hierarchical regression model. Using sex-specific regression equations, 87.7% of the boys and 83.7% of the girls had a predicted %BF within 3% units of the %BF obtained by DXA.

Conclusion: In pre-pubertal children, pQCT measures of adiposity are strongly associated with whole-body per cent body fat. This reproducible method could be an alternative technique to estimate body composition in this population.

Neighbourhood physical activity environments and adiposity in children and mothers : a three-year longitudinal study

Background Although neighbourhood environments are often blamed for contributing to rising levels of obesity, current evidence is based predominantly on cross-sectional samples. This study examined associations between objectively-measured environmental characteristics of neighbourhoods and adiposity cross-sectionally and longitudinally over three years in children and their female carers.

Methods Longitudinal study of 140 5-6 year-old and 269 10-12 year-old children and their female carers (n = 369). At baseline (2001) and follow-up (2004), height and weight were measured among children and self-reported among female carers, and were used to compute BMI z-scores and BMI, respectively. A Geographic Information System determined access to destinations (public open spaces, sports options, walking/cycling tracks), road connectivity (density of cul-de-sacs and intersections, proportion of 4-way intersections, length of 'access' paths (overpasses, access lanes, throughways between buildings)) and traffic exposure (length of 'busy' and 'local' roads) within 800 m and 2 km of home. Univariate and multivariable linear regression analyses examined associations between environmental characteristics and BMI/BMI z-scores at baseline and change in BMI/BMI z-scores over the three years.

Results Cross-sectionally, BMI z-score was inversely associated with length (km) of access paths within 800 m (b = -0.50) and 2 km (b = -0.16) among younger and number of sport/recreation public open spaces (b = -0.14) and length (km) of 'access' paths (b = -0.94) within 800 m and length of local roads within 2 km (b = -0.01) among older children. Among female carers, BMI was associated with length (km) of walking/cycling tracks (b = 0.17) and busy roads (b = -0.34) within 800 m. Longitudinally, the proportion of intersections that were 4-way (b = -0.01) within 800 m of home was negatively associated with change in BMI z-score among younger children, while length (km) of access paths (b = 0.18) within 800 m was significant among older children. Among female carers, options for aerobics/fitness and swimming within 2 km were associated with change in BMI (B = -0.42).

Conclusion A small number of neighbourhood environment features were associated with adiposity outcomes. These differed by age group and neighbourhood scale (800 m and 2 km) and were inconsistent between cross-sectional and longitudinal findings. However, the results suggest that improvements to road connectivity and slowing traffic and provision of facilities for leisure activities popular among women may support obesity prevention efforts.

Bipolar disorder and adiposity : a study using whole body dual energy X-ray absorptiometry scans

Objective: Previous research has demonstrated a relationship between adiposity and bipolar disorder, although data are derived predominantly from patient samples and use indirect methods of assessing adiposity. This study investigated the association between bipolar disorder and several indices of adiposity, including body fat mass as measured by dual energy X-ray absorptiometry (DXA), in a community-based sample.

Methods: In this study, 21 women with bipolar disorder and 523 healthy controls were drawn from an age-stratified, random, community-based sample of women (20–93 years) participating in the Geelong Osteoporosis Study. Bipolar disorder was diagnosed utilising a semi-structured clinical interview. Anthropometric measurements (weight, height, waist and hip circumference) were taken and fat mass was determined from whole body DXA scans (Lunar DPX-L).

Results: Those with bipolar disorder tended to have greater adiposity. Age-adjusted mean (95% CI) values for bipolar versus controls according to adiposity indices were weight 75.6 (68.9–82.3) versus 72.6 (71.3–74.0) kg, waist circumference 89.8 (84.1–95.6) versus 87.3 (86.1–88.5) cm, waist:hip ratio 0.85 (0.82–0.87) versus 0.84 (0.83–0.84), body mass index 27.6 (25.1–30.1) versus 27.5 (27.0–28.0) kg/m2, fat mass 31.4 (26.5–36.3) versus 28.6 (27.5–29.5) kg and %body fat 40.4 (36.9–43.9) versus 38.0 (37.3–38.7)%; all p > 0.05. Further adjustment for height, smoking, alcohol, psychotropic medication, energy intake or physical activity did not influence these patterns.

Conclusion: Although a pattern suggestive of greater adiposity among those with bipolar disorder was observed, no significant differences were detected. We cannot exclude the possibility of a type II error. Further research with a larger sample may produce more conclusive results.

Scores on the dietary guideline index for children and adolescents are associated with nutrient intake and socio-economic position but not adiposity 1-3

Diet quality indices reflect overall dietary patterns better than single nutrients or food groups. The study aims were to develop a measure of adherence with dietary guidelines applicable to child and adolescent populations in Australia and determine the association between index scores and food and nutrient intake, socio-demographic characteristics, and measures of adiposity. Data were analyzed from 4- to 16-y-old participants of the 2007 Australian Children’s Nutrition and Physical Activity Survey (n = 3416). The Dietary Guideline Index for Children and Adolescents (DGI-CA) comprises 11 components: 5 core food groups, wholegrain bread, reduced-fat dairy foods, extra foods (nutrient poor and high in fat, salt, and added sugar), healthy fats/oils, water, and diet variety (possible score of 100). The index criteria were age specific. The mean DGI-CA score was low (53.6 ± 0.4), similar between boys and girls, and differed by age; the youngest children scored higher than the oldest children (P < 0.0001). Higher DGI-CA scores were associated with lower energy intake, energy density, total and saturated fat, and sugar intake; higher protein, carbohydrate, fiber, calcium, iron, vitamin C, vitamin A, folate, phosphorous, magnesium, zinc, and iodine intakes; and a higher polyunsaturated:saturated fat ratio (P < 0.0001). DGI-CA scores were associated with socio-economic characteristics and measures of family circumstance. Weak positive associations were observed between DGI-CA score and BMI or waist circumference Z-scores in the 4- to 10-y and 12- to 16-y age groups only. This index is the first validated index in Australia and one of the few international indices to describe the diet quality of children and adolescents.

Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.