Kathryn Backholer

Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells.

Kisspeptin stimulates reproduction, and kisspeptin cells in the arcuate nucleus (ARC) express Ob-Rb in the mouse. Herein we report studies in ewes to determine whether kisspeptin cells express Ob-Rb and respond to leptin and whether reciprocal connections exist between kisspeptin cells and proopiomelanocortin (POMC) or neuropeptide Y (NPY) cells to modulate reproduction and metabolic function. Kiss1 mRNA was measured by in situ hybridization in ovariectomized ewes that were normal body weight, lean, or lean with leptin treatment by intracerebroventricular (icv) infusion (4 microg/h, 3 d). Kiss1 expression in the ARC and the preoptic area was lower in hypogonadotropic lean animals than animals of normal weight, and icv infusion of leptin partially restored Kiss1 expression in lean animals. Single-cell laser capture microdissection coupled with real-time PCR showed that Kiss1 cells in the preoptic area and ARC express Ob-Rb. Double-label fluorescent immunohistochemistry showed that reciprocal connections exist between kisspeptin cells and NPY and POMC cells. Accordingly, we treated ovariectomized ewes with kisspeptin (5 microg/h, icv) or vehicle for 20 h and examined POMC and NPY gene expression by in situ hybridization. Kisspeptin treatment reduced POMC and increased NPY gene expression. Thus, kisspeptin neurons respond to leptin and expression of Kiss1 mRNA is affected by leptin status. Kisspeptin cells communicate with NPY and POMC cells, altering expression of the relevant genes in the target cells; reciprocal connections also exist. This network between the three cell types could coordinate brain control of reproduction and metabolic homeostatic systems.

Diabetes and risk of physical disability in adults: a systematic review and meta-analysis

BACKGROUND According to previous reports, the risk of disability as a result of diabetes varies from none to double. Disability is an important measure of health and an estimate of the risk of disability as a result of diabetes is crucial in view of the global diabetes epidemic. We did a systematic review and meta-analysis to estimate this risk. METHODS We searched Ovid, Medline, Embase, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature up to Aug 8, 2012. We included studies of adults that compared the risk of disability-as measured by activities of daily living (ADL), instrumental activities of daily living (IADL), or mobility-in people with and without any type of diabetes. We excluded studies of subpopulations with specific illnesses or of people in nursing homes. From the studies, we recorded population characteristics, how diabetes was diagnosed (by doctor or self-reported), domain and definition of disability, and risk estimates for disability. We calculated pooled estimates by disability type and type of risk estimate (odds ratio [OR] or risk ratio [RR]). RESULTS Our systematic review returned 3224 results, from which 26 studies were included in our meta-analyses. Diabetes increased the risk of mobility disability (15 studies; OR 1.71, 95% CI 1.53-1.91; RR 1.51, 95% CI 1.38-1.64), of IADL disability (ten studies; OR 1.65, 95% CI 1.55-1.74), and of ADL disability (16 studies; OR 1.82, 95% CI 1.63-2.04; RR 1.82, 95% CI 1.40-2.36). INTERPRETATION Diabetes is associated with a strong increase in the risk of physical disability. Efforts to promote healthy ageing should account for this risk through prevention and management of diabetes. FUNDING Monash University, Baker IDI Bright Sparks Foundation, Australian Postgraduate Award, VicHealth, National Health and Medical Research Council, Australian Research Council, Victorian Government.

Melanocortins May Stimulate Reproduction by Activating Orexin Neurons in the Dorsomedial Hypothalamus and Kisspeptin Neurons in the Preoptic Area of the Ewe

To further test the hypothesis that melanocortins stimulate the reproductive axis, we treated ewes with melanocortin agonist (MTII) in the luteal phase of the estrous cycle and during seasonal anestrus. Lateral ventricular infusion of MTII (10 microg/h) during the luteal phase increased LH secretion. Retrograde neuronal tracing in the brain showed few proopiomelanocortin or kisspeptin cells in the arcuate nucleus, but more than 70% of kisspeptin cells in the dorsolateral preoptic area (POA), projecting to the ventromedial POA in which GnRH cells are located. MTII infusion (20 h) was repeated in luteal phase ewes and brains were harvested to measure gene expression of preproorexin and kisspeptin. Expression of orexin in the dorsomedial hypothalamus and kisspeptin in the POA was up-regulated by MTII treatment and Kiss1 in the arcuate nucleus was down-regulated. Seasonally anestrous ewes were progesterone primed and then treated (lateral ventricular) with MTII (10 microg/h) or vehicle for 30 h, and blood samples were collected every 2 h from 4 h before infusion until 6 h afterward to monitor acute response in terms of LH levels. A rise in basal LH levels was seen, but samples collected around the time of the predicted LH surge did not indicate that an ovulatory event occurred. We conclude that melanocortins are positive regulators of the reproductive neuroendocrine system, but treatment with melanocortins does not fully overcome seasonal acyclicity. The stimulatory effect of melanocortin in the luteal phase of the estrous cycle may be via the activation of kisspeptin cells in the POA and/or orexin cells in the dorsomedial hypothalamus.

Projected Progression of the Prevalence of Obesity in Australia

Several country‐specific and global projections of the future obesity prevalence have been conducted. However, these projections are obtained by extrapolating past prevalence of obesity or distributions of body weight. More accurate would be to base estimates on the most recent measures of weight change. Using measures of overweight and obesity incidence from a national, longitudinal study, we estimated the future obesity prevalence in Australian adults. Participants were adults aged ≥25 years in 2000 participating in the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study (baseline 2000, follow‐up 2005). In this population, approximately one‐fifth of those with normal weight or overweight progressed to a higher weight category within 5 years. Between 2000 and 2025, the adult prevalence of normal weight was estimated to decrease from 40.6 to 28.1% and the prevalence of obesity to increase from 20.5 to 33.9%. By the time, those people aged 25–29 in 2000 reach 60–64 years, 22.1% will be normal weight, and 42.4% will be obese. On average, normal‐weight females aged 25–29 years in 2000 will live another 56.2 years: 26.6 years with normal weight, 15.6 years with overweight, and 14.0 years with obesity. Normal‐weight males aged 25–29 years in 2000 will live another 51.5 years: 21.6 years with normal weight, 21.1 years with overweight, and 8.8 years with obesity. If the rates of weight gain observed in the first 5 years of this decade are maintained, our findings suggest that normal‐weight adults will constitute less than a third of the population by 2025, and the obesity prevalence will have increased by 65%.

The effect of obesity prevention interventions according to socioeconomic position: a systematic review

Obesity prevention is a major public health priority. It is important that all groups benefit from measures to prevent obesity, but we know little about the differential effectiveness of such interventions within particular population subgroups. This review aimed to identify interventions for obesity prevention that evaluated a change in adiposity according to socioeconomic position (SEP) and to determine the effectiveness of these interventions across different socioeconomic groups. A systematic search of published and grey literature was conducted. Studies that described an obesity prevention intervention and reported anthropometric outcomes according to a measure of SEP were included. Evidence was synthesized using narrative analysis. A total of 14 studies were analysed, representing a range of study designs and settings. All studies were from developed countries, with eight conducted among children. Three studies were shown to have no effect on anthropometric outcomes and were not further analysed. Interventions shown to be ineffective in lower SEP participants were primarily based on information provision directed at individual behaviour change. Studies that were shown to be effective in lower SEP participants primarily included community‐based strategies or policies aimed at structural changes to the environment. Interventions targeting individual‐level behaviour change may be less successful in lower SEP populations. It is essential that our efforts to prevent obesity do not leave behind the most disadvantaged members of society.

Obesity and trends in life expectancy

Background. Increasing levels of obesity over recent decades have been expected to lead to an epidemic of diabetes and a subsequent reduction in life expectancy, but instead all-cause and cardiovascular-specific mortality rates have decreased steadily in most developed countries and life expectancy has increased. Methods. This paper suggests several factors that may be masking the effects of obesity on life expectancy. Results. It is possible that health and life expectancy gains could be even greater if it was not for the increasing prevalence of extreme obesity. It is also possible that the principal impact of obesity is on disability-free life expectancy rather than on life expectancy itself. Conclusion. If the principal impact of obesity were through disability-free life expectancy rather than on life expectancy itself, this would have substantial implications for the health of individuals and the future burden on the health care system.

Increasing body weight and risk of limitations in activities of daily living: a systematic review and meta-analysis

This study examined the relationship between normal weight, overweight and obesity class I and II+, and the risk of disability, which is defined as impairment in activities of daily living (ADL). Systematic searching of the literature identified eight cross‐sectional studies and four longitudinal studies that were comparable for meta‐analysis. An additional four cross‐sectional studies and one longitudinal study were included for qualitative review. Results from the meta‐analysis of cross‐sectional studies revealed a graded increase in the risk of ADL limitations from overweight (1.04, 95% confidence interval [CI] 1.00–1.08), class I obesity (1.16, 95% CI 1.11–1.21) and class II+ obesity (1.76, 95% CI 1.28–2.41), relative to normal weight. Meta‐analyses of longitudinal studies revealed a similar graded relationship; however, the magnitude of this relationship was slightly greater for all body mass index categories. Qualitative analysis of studies that met the inclusion criteria but were not compatible for meta‐analysis supported the pooled results. No studies identified met all of the pre‐defined quality criteria, and subgroup analysis was inhibited due to insufficient comparable studies. We conclude that increasing body weight increases the risk of disability in a graded manner, but also emphasize the need for additional studies using contemporary longitudinal cohorts with large numbers of obese class III individuals, a range of ages and with measured height and weight, and incident ADL questions.

Impact of a pedometer-based workplace health program on cardiovascular and diabetes risk profile

OBJECTIVE To evaluate whether participation in a four-month, pedometer-based, physical activity, workplace health programme results in an improvement in risk factors for diabetes and cardiovascular disease. METHODS Adults employed within Australia in primarily sedentary occupations and voluntarily enrolled in a workplace programme, the Global Corporate Challenge®, aimed at increasing physical activity were recruited. Data included demographic, behavioural, anthropometric and biomedical measurements. Measures were compared between baseline and four-months. RESULTS 762 participants were recruited in April/May 2008 with 79% returning. Improvements between baseline and four-months amongst programme participants were observed for physical activity (an increase of 6.5% in the proportion meeting guidelines, OR(95%CI): 1.7(1.1, 2.5)), fruit intake (4%, OR: 1.7(1.0, 3.0)), vegetable intake (2%, OR: 1.3(1.0, 1.8)), sitting time (-0.6(-0.9, -0.3) hours/day), blood pressure (systolic: -1.8(-3.1, -.05) mmHg; diastolic: -1.8(-2.4, -1.3) mmHg) and waist circumference (-1.6(-2.4, -0.7) cm). In contrast, an increase was found for fasting total cholesterol (0.3(0.1, 0.4) mmol/L) and triglycerides (0.1(0.0, 0.1) mmol/L). CONCLUSION Completion of this four-month, pedometer-based, physical activity, workplace programme was associated with improvements in behavioural and anthropometric risk factors for diabetes and cardiovascular disease. Long-term evaluation is required to evaluate the potential of such programmes to prevent the onset of chronic disease.

A framework for evaluating the impact of obesity prevention strategies on socioeconomic inequalities in weight

We developed a theoretical framework to organize obesity prevention interventions by their likely impact on the socioeconomic gradient of weight. The degree to which an intervention involves individual agency versus structural change influences socioeconomic inequalities in weight. Agentic interventions, such as standalone social marketing, increase socioeconomic inequalities. Structural interventions, such as food procurement policies and restrictions on unhealthy foods in schools, show equal or greater benefit for lower socioeconomic groups. Many obesity prevention interventions belong to the agento-structural types of interventions, and account for the environment in which health behaviors occur, but they require a level of individual agency for behavioral change, including workplace design to encourage exercise and fiscal regulation of unhealthy foods or beverages. Obesity prevention interventions differ in their effectiveness across socioeconomic groups. Limiting further increases in socioeconomic inequalities in obesity requires implementation of structural interventions. Further empirical evaluation, especially of agento-structural type interventions, remains crucial.

Trends in child and adolescent obesity prevalence in economically advanced countries according to socioeconomic position: a systematic review

Recent obesity trends in children and adolescents suggest a plateau. However, it is unclear whether such trends have been experienced across socioeconomic groups. We analysed whether recent trends in child and adolescent overweight and obesity differ by socioeconomic position (SEP) across economically advanced countries. Eligible studies reported overweight and obesity prevalence in children and/or adolescents (2–18 years), for at least two time points since 1990, stratified by SEP. Socioeconomic differences in trends in child and adolescent overweight and obesity over time were analysed. Differences in trends between SEP groups were observed across a majority of studies. Over half the studies indicated increasing prevalence among low SEP children and adolescents compared to a third of studies among children and adolescents with a high SEP. Around half the studies indicated widening socioeconomic inequalities in overweight and obesity. Since 2000 a majority of studies demonstrated no change or a decrease in prevalence among both high and low SEP groups. However around 40% of studies indicated widening of socioeconomic inequalities post‐2000. While our study provides grounds for optimism, socioeconomic inequalities in overweight and obesity continue to widen. These findings highlight the need for greater consideration of different population groups when implementing obesity interventions.