Progression of cardiovascular and endocrine dysfunction in a rabbit model of obesity

In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n¼23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15±3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP p80mmHg, MAP had increased by 8.1±1.3, 4.7±1.7 and 5.6±1.2mmHg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6±1.5, 3.0±1.7 and 3.9±1.4mmHg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline 480mmHg. Plasma concentrations of leptin and insulin increased during the first 3–6 weeks of fat feeding and then stabilized (increasing by 111±17% and 731±302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertensionand tachycardia in the rabbit model of obesity.

Processing and excellent oxidation resistance of nanocrystalline Fe-Cr alloys

Nanocrystalline and microcrystalline Fe-10Cr alloys were prepared by high energy ball milling followed by compaction and sintering, and then oxidized in air for 52 hours at 400ºC. The oxidation resistance of nanocrystalline Fe-10Cr alloy as determined by measuring the weight gain after regular time intervals was compared with that of the microcrystalline alloy of same chemical composition (also prepared by the same processing route and oxidized under identical conditions). Oxidation resistance of nanocrystalline Fe10Cr alloy was found to be in excess of an order of magnitude superior than that of microcrystalline Fe10Cr alloy. The paper also presents results of secondary ion mass spectrometry of oxidized samples of nanocrystalline and microcrystalline Fe-Cr alloys, evidencing the formation of a more protective oxide scale in the nanocrystalline alloy.

Associations between measures of adiposity over 10 years and patella cartilage in population-based asymptomatic women

Objective: Osteoarthritis (OA) most commonly affects the patellofemoral compartment of the knee, and is a major cause of pain and disability. Structural changes that evolve prior to the onset of symptoms can be visualised using magnetic resonance imaging (MRI). There is little known information about the role of adiposity on the early structural changes in the patella cartilage in younger, asymptomatic adult females.

Methods: One hundred and sixty asymptomatic women (20–49 years) participating in the Geelong Osteoporosis Study underwent knee MRI (2006–8). Weight and body mass index (BMI) were measured 10 years prior (1994–7, baseline) and at the time of MRI (current), with change over the period calculated (current–baseline). Relationships between measures of adiposity and patella cartilage volume and defects were examined.

Results: After adjustment for age and patella bone volume, there was a reduction of 13 ml (95% confidence interval (95% CI), −25.7, −0.55) in patella cartilage volume for every 1 unit increase in current BMI, and a reduction of 27 ml (95% CI −52.6, −1.5) per BMI unit increase over 10 years (P=0.04 for both). No significant association was observed between baseline BMI and patella cartilage volume (P=0.16). Increased baseline and current weight and BMI were associated with increased prevalence of patella cartilage defects (all P<0.001).

Conclusions: Adiposity and weight gain during midlife are associated with detrimental structural change at the patella in young to middle-aged healthy non-osteoarthritic women. Maintaining a healthy weight and avoiding weight gain in younger asymptomatic women may be important in the prevention of patellofemoral OA.

Acculturation and obesity among migrant populations in high income countries - a systematic review

Background:
There is evidence to suggest that immigrant populations from low or medium-income countries to high income countries show a significant change in obesogenic behaviors in the host society, and that these changes are associated with acculturation. However, the results of studies vary depending on how acculturation is measured. The objective of this study is to systematically review the evidence on the relationship between acculturation - as measured with a standardized acculturation scale - and overweight/obesity among adult migrants from low/middle countries to high income countries.

Methods:

Associations between child temperament, maternal feeding practices and child body mass index during the preschool years: a systematic review of the literature

It is a research priority to identify modifiable risk factors to improve the effec- tiveness of childhood obesity prevention strategies. Research, however, has largely overlooked the role of child temperament and personality implicated in obesogenic risk factors such as maternal feeding and body mass index (BMI) of preschoolers. A systematic review of relevant literature was conducted to inves- tigate the associations between child temperament, child personality, maternal feeding and BMI and/or weight gain in infants and preschoolers; 18 papers were included in the review. The findings revealed an association between the temperament traits of poor self-regulation, distress to limitations, low and high soothability, low negative affectivity and higher BMI in infants and preschool- aged children. Temperament traits difficult, distress to limitations, surgency/ extraversion and emotionality were significantly associated with weight gain rates in infants. The results also suggested that child temperament was associated with maternal feeding behaviours that have been shown to influence childhood over- weight and obesity, such as using restrictive feeding practices with children per- ceived as having poor self-regulation and feeding potentially obesogenic food and drinks to infants who are more externalizing. Interestingly, no studies to date have evaluated the association between child personality and BMI/weight gain in infants and preschoolers. There is a clear need for further research into the association of child temperament and obesogenic risk factors in preschool-aged children.

Process evaluation of a community-based intervention program: Healthy Youth Healthy Communities, an adolescent obesity prevention project in Fiji

Nearly one-half of the adult population in Fiji between the ages of 15–64 years is either overweight or obese; and rates amongst school children have, on average, doubled during the last decade. There is an urgent need to scale up the promotion of healthy behaviors and environments using a multi-sectoral approach. The Healthy Youth Healthy Community (HYHC) project in Fiji used a settings approach in secondary schools and faith-based organizations to increase the capacity of the whole community, including churches, mosques and temples, to promote healthy eating and regular physical activity, and to prevent unhealthy weight gain in adolescents aged 13–18 years. The team consisted of a study manager, project coordinator and four research assistants (RAs) committed to planning, designing and facilitating the implementation of intervention programs in collaboration with other stakeholders, such as the wider school communities, government and non-governmental organizations and business partners. Process data were collected on all intervention activities and analyzed by dose, frequency and reach for each specific strategy. The Fiji Action Plan included nine objectives for the school settings; four were based on nutrition and two on physical activity in schools, plus three general objectives, namely capacity building, social marketing and evaluation. Long-term change in nutritional behavior was difficult to achieve; a key contributor to this was the unhealthy food served in the school canteens. Whilst capacity-building proved to be one of the best mechanisms for intervening, it is important to consider the cultural and social factors influencing health behaviors and affecting specific groups.

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 μg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: −54%, paraventricular: −69%, and dorsomedial hypothalamus: −65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked “selective leptin resistance” in these animals.

The impact of interventions to prevent obesity or improve obesity related behaviours in children (0-5 years) from socioeconomically disadvantaged and/or indigenous families: a systematic review

Background
Children from disadvantaged families including those from low socioeconomic backgrounds and Indigenous families have higher rates of obesity, making early intervention a priority. The aim of this study was to systematically review the literature to examine the effectiveness of interventions to prevent obesity or improve obesity related behaviours in children 0-5 years from socioeconomically disadvantaged or Indigenous families.

Methods
Searches of major electronic databases identified articles published from 1993–2013 targeting feeding practices, anthropometric, diet, activity or sedentary behaviour outcomes. This was supplemented with snowballing from existing reviews and primary studies. Data extraction was undertaken by one author and cross checked by another. Quality assessments included both internal and external validity.

Results
Thirty-two studies were identified, with only two (both low quality) in Indigenous groups. Fourteen studies had a primary aim to prevent obesity. Mean differences between intervention and control groups ranged from -0.29 kg/m2 to -0.54 kg/m2 for body mass index (BMI) and -2.9 to -25.6% for the prevalence of overweight/obesity. Interventions initiated in infancy (under two years) had a positive impact on obesity related behaviours (e.g. diet quality) but few measured the longer-term impact on healthy weight gain. Findings amongst pre-schoolers (3–5 years) were mixed, with the more successful interventions requiring high levels of parental engagement, use of behaviour change techniques, a focus on skill building and links to community resources. Less than 10% of studies were high quality. Future studies should focus on improving study quality, including follow-up of longer-term anthropometric outcomes, assessments of cost effectiveness, acceptability in target populations and potential for implementation in routine service delivery.

Conclusion
There is an urgent need for further research on effective obesity prevention interventions for Indigenous children. The findings from the growing body of intervention research focusing on obesity prevention amongst young children from socioeconomically disadvantaged families suggest intervention effects are modest but promising. Further high quality studies with longer term follow up are required.

International study of objectively measured physical activity and sedentary time with body mass index and obesity: IPEN adult study

BACKGROUND: Physical activity (PA) has been consistently implicated in the etiology of obesity, whereas recent evidence on the importance of sedentary time remains inconsistent. Understanding of dose-response associations of PA and sedentary time with overweight and obesity in adults can be improved with large-scale studies using objective measures of PA and sedentary time. The purpose of this study was to examine the strength, direction and shape of dose-response associations of accelerometer-based PA and sedentary time with body mass index (BMI) and weight status in 10 countries, and the moderating effects of study site and gender. METHODS: Data from the International Physical activity and the Environment Network (IPEN) Adult study were used. IPEN Adult is an observational multi-country cross-sectional study, and 12 sites in 10 countries are included. Participants wore an accelerometer for seven consecutive days, completed a socio-demographic questionnaire and reported height and weight. In total, 5712 adults (18-65 years) were included in the analyses. Generalized additive mixed models, conducted in R, were used to estimate the strength and shape of the associations. RESULTS: A curvilinear relationship of accelerometer-based moderate-to-vigorous PA and total counts per minute with BMI and the probability of being overweight/obese was identified. The associations were negative, but weakened at higher levels of moderate-to-vigorous PA (>50 min per day) and higher counts per minute. No associations between sedentary time and weight outcomes were found. Complex site- and gender-specific findings were revealed for BMI, but not for weight status. CONCLUSIONS: On the basis of these results, the current Institute of Medicine recommendation of 60 min per day of moderate-to-vigorous PA to prevent weight gain in normal-weight adults was supported. No relationship between sedentary time and the weight outcomes was present, calling for further examination. If moderator findings are confirmed, the relationship between PA and BMI may be country- and gender-dependent, which could have important implications for country-specific health guidelines. © 2015 Macmillan Publishers Limited All rights reserved.

The role of obesity duration on the association between obesity and risk of physical disability

Objective To relate measured obesity duration in mid-life with subsequent incidence of physical disability over and above body mass index (BMI) attained. Methods Framingham Offspring Study is a longitudinal study that began in 1971. Examination 5 (1991-1995; "baseline") and disability onset ascertained from examinations 6-8 (2008) were used. About 2,095 disability-free participants aged 45-65 years at baseline were included. Obesity (BMI- ≥- 30 kg/m2) duration was calculated between examination 1 and examination 5. Cox regression was used to analyze time to disability. Results 204 participants developed disability (incidence rate = 7.9 per 1,000 person-years). Obesity duration ranged from 0 to 22 years (mean of 2.0 years overall, 8.3 years for those with baseline obesity). Obesity duration increased risk of new disability (hazard ratio [HR] 1.07 per year of obesity; 95% confidence interval [CI] 1.05-1.09). This association was attenuated on further adjustment for baseline BMI (HR 1.03; 95% CI 1.00-1.06). Conclusions Being obese for longer during mid-life increases the risk of later-life disability over and above attained BMI. These results support the need for prevention of weight gain in young adults to avoid an increasing burden of physical disability in later life.

Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions.

Duloxetine: a review.

A developing concept is that antidepressant strategies which combine multiple mechanisms of action may have advantages over agents with single mechanisms. Duloxetine is a novel potent dual reuptake inhibitor of noradrenaline and serotonin. The antidepressant efficacy of duloxetine is reviewed in three trials. Results that emerge confirm the acute efficacy of the agent in major depressive disorder. In particular, remission rates in the comparative trials are higher with duloxetine than with either paroxetine or fluoxetine. Duloxetine appears to have specific efficacy in patients with somatic symptoms and there is some clinical evidence of analgesic properties. Modest weight loss was consistently described in the three acute trials and modest weight gain was seen in an open label follow-up study. Duloxetine was well-tolerated in all three trials with similar patterns of adverse events. No significant safety issues emerged from these trials.