Effect of diet versus diet and exercise on weight loss and body composition in class II and III obesity: A systematic review

Class II and III obesity (BMI >35 kg·m2) have increased dramatically in recent years. Current clinical guidelines suggest diet and exercise as first line treatment for adults throughout the spectrum of overweight and obesity. However, to date there is no systematic review that examines the effects of diet and exercise on this high risk population. This systematic review will examine the combined effects of diet versus diet and exercise on body composition in severe obesity. Medline and Cinahl were searched for randomised controlled trials comparing diet and exercise to diet alone. Studies published until July 2013 were included if they used reliable methods for analysing body composition in adults with BMI ≥ 35 kg·m2. Five of 459 studies met the inclusion criteria. Two studies, both in older adults, reported that exercise reduced lean mass loss during weight loss. Two studies showed that exercise facilitated (greater) fat mass loss. The remaining study reported no differences in body composition when exercise is added to energy restriction. Exercise training during energy restriction for individuals with BMI ≥35 kg.m2 may influence body composition outcomes but the evidence is limited. Further studies should focus on the efficacy of different exercise protocols during energy restriction for this population in order to better inform decision making for the treatment of severe obesity in respect to favourable body composition outcomes.

Prevalence of class-I, class-II and class-III obesity in Australian adults between 1995 and 2011-12

OBJECTIVE: To compare the prevalence of class-I, II and III obesity in Australian adults between 1995, 2007-08 and 2011-12. METHODS: Prevalence data for adults (aged 18+ years) were sourced from customised data from the nationally representative National Nutrition Survey (1995), the National Health Survey (2007-08), and the Australian Health Survey (2011-12) conducted by the Australian Bureau of Statistics. Obesity classifications were based on measured height and weight (class-I body mass index: 30.0-34.9kg/m(2), class-II: 35.0-39.9kg/m(2) and class-III: ≥40.0kg/m(2)). Severe obesity was defined as class-II or class-III obesity. RESULTS: Between 1995 and 2011-12, the prevalence of obesity (all classes combined) increased from 19.1% to 27.2%. During this 17 year period, relative increases in class I, II and III obesity were 1.3, 1.7 and 2.2-fold respectively. In 2011-12, the prevalence of class I, II and III obesity was 19.4, 5.9 and 2.0 per cent respectively in men, and 16.1, 6.9 and 4.2 per cent respectively in women. One in every ten people was severely obese, increasing from one in twenty in 1995, and women were disproportionally represented in this population. Obesity prevalence increased with increasing levels of area-level socioeconomic disadvantage, particularly for the more severely obese classes. Severe obesity affected 6.2% and 13.4% in the least and most disadvantaged quintiles respectively. CONCLUSION: Over the last two decades, there have been substantial increases in the prevalence of obesity, particularly the more severe levels of obesity. This study highlights high risk groups who warrant targeted weight gain prevention interventions.

Turnover of bone marrow-derived cells in the irradiated mouse cornea

In light of an increasing awareness of the presence of bone marrow (BM)-derived macrophages in the normal cornea and their uncertain role in corneal diseases, it is important that the turnover rate of these resident immune cells be established. The baseline density and distribution of macrophages in the corneal stroma was investigated in Cx3cr1gfp transgenic mice in which all monocyte-derived cells express enhanced green fluorescent protein (eGFP). To quantify turnover, BM-derived cells from transgenic eGFP mice were transplanted into whole-body irradiated wild-type recipients. Additionally, wild-type BM-derived cells were injected into irradiated Cx3cr1+/gfp recipients, creating reverse chimeras. At 2, 4 and 8 weeks post-reconstitution, the number of eGFP+ cells in each corneal whole mount was calculated using epifluorescence microscopy, immunofluorescence staining and confocal microscopy. The total density of myeloid-derived cells in the normal Cx3cr1+/gfp cornea was 366 cells/mm2. In BM chimeras 2 weeks post-reconstitution, 24% of the myeloid-derived cells had been replenished and were predominantly located in the anterior stroma. By 8 weeks post-reconstitution 75% of the myeloid-derived cells had been replaced and these cells were distributed uniformly throughout the stroma. All donor eGFP+ cells expressed low to moderate levels of CD45 and CD11b, with approximately 25% coexpressing major histocompatibility complex class II, a phenotype characteristic of previous descriptions of corneal stromal macrophages. In conclusion, 75% of the myeloid-derived cells in the mouse corneal stroma are replenished after 8 weeks. These data provide a strong basis for functional investigations of the role of resident stromal macrophages versus non-haematopoietic cells using BM chimeric mice in models of corneal inflammation.

Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rates of replenishment in bone marrow chimeric mice

The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx3cr1 knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX3CR1 on their number and tissue distribution. Iba-1 major histocompatibility complex (MHC) Class II CD169 CD68 macrophages and CD11c putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx3cr1 mice did not reveal CX3CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx3cr1/-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX3CR1-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.

CD1d-restricted NKT cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses

CD1d-restricted NKT cells are a novel T cell lineage with unusual features. They co-express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN- and IL-4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d-restricted NKT cell activation in the induction of B cell-mediated immune responses to infection is still unclear. We show here that CD1-restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite-specific antibody formation in response to Plasmodium berghei infection. The increased B cell-mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)-anchored protein merozoite surface protein 1 (MSP-1) were found to be significantly lower in CD1-/- mice compared to wild-type animals. P. berghei-infected MHC class II (MHCII)-/- mice also generated antibodies against MSP-1, suggesting that antibody production against GPI-anchored antigens in response to malaria infection can arisefrom both MHCII-dependent and independent pathways.

Systemic activation of dendritic cells by toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

The mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. Here we show that infection with a malaria parasite (Plasmodium berghei) or simple systemic exposure to bacterial or viral Toll-like receptor ligands inhibited cross-priming. Reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit T cell proliferation. Although activated dendritic cells retained their capacity to present viral antigens via the endogenous major histocompatibility complex class I processing pathway, antiviral responses were greatly impaired in mice exposed to Toll-like receptor ligands. This is consistent with a key function for cross-presentation in antiviral immunity and helps explain the immunosuppressive effects of systemic infection. Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections.

Membrane nanotubes in myeloid cells in the adult mouse cornea represent a novel mode of immune cell interaction

Membrane nanotubes (MNTs) are newly discovered cellular extensions that are either blind-ended or can connect widely separated cells. They have predominantly been investigated in cultured isolated cells, however, previously we were the first group to demonstrate the existence of these structures in vivo in intact mammalian tissues. We previously demonstrated the frequency of both cell–cell or bridging MNTs and blind-ended MNTs was greatest between major histocompatibility complex (MHC) class II+ cells during corneal injury or TLR ligand-mediated inflammation. The present study aimed to further explore the dynamics of MNT formation and their size, presence in another tissue, the dura mater, and response to stress factors and an active local viral infection of the murine cornea. Confocal live cell imaging of myeloid-derived cells in inflamed corneal explants from Cx3cr1GFP and CD11ceYFP transgenic mice revealed that MNTs form de novo at a rate of 15.5 μm/min. This observation contrasts with previous studies that demonstrated that in vitro these structures originate from cell–cell contacts. Conditions that promote formation of MNTs include inflammation in vivo and cell stress due to serum starvation ex vivo. Herpes simplex virus-1 infection did not cause a significant increase in MNT numbers in myeloid cells in the cornea above that observed in injury controls, confirming that corneal epithelium injury alone elicits MNT formation in vivo. These novel observations extend the currently limited understanding of MNTs in live mammalian tissues.

Exercise and MEF2–HDAC interactions.

Exercise increases the metabolic capacity of skeletal muscle, which improves whole-body energy homeostasis and contributes to the positive health benefits of exercise. This is, in part, mediated by increases in the expression of a number of metabolic enzymes, regulated largely at the level of transcription. At a molecular level, many of these genes are regulated by the class II histone deacetylase (HDAC) family of transcriptional repressors, in particular HDAC5, through their interaction with myocyte enhancer factor 2 transcription factors. HDAC5 kinases, including 5′-AMP-activated protein kinase and protein kinase D, appear to regulate skeletal muscle metabolic gene transcription by inactivating HDAC5 and inducing HDAC5 nuclear export. These mechanisms appear to participate in exercise-induced gene expression and could be important for skeletal muscle adaptations to exercise.

Utility-based quality of life associated with overweight and obesity : the Australian diabetes, obesity, and lifestyle study

This study aimed to estimate utility-based quality of life (UQoL) differences between healthy body weight and excess body weight categories. Cross-sectional analysis of 10,959 adults, participating in baseline data collection of the nationally representative Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study was undertaken. Height and weight were measured by trained personnel. Body weight categories were assigned as healthy weight, overweight, and obesity subclasses I, II and III. UQoL was assessed using the SF-6D, which captures physical functioning, role limitation, social functioning, pain, mental health, and vitality on a score of 0.00–1.00 (worst-best). The relationship between body weight categories and UQoL was assessed using linear regression, adjusting for age, sex, education, and smoking. Relative to the healthy weight group (mean UQoL score 0.77), mean adjusted UQoL differences (95% confidence intervals) were 0.001 (−0.008, 0.010) for overweight, −0.012 (−0.022, −0.001) for class-I obese, −0.020 (−0.041, 0.001) for class-II obese, and −0.069 (−0.099, −0.039) for class-III obese groups. Adding metabolic syndrome markers to the covariates had little impact on these differences. Results confirmed an inverse dose–response relationship between body weight and UQoL in this study of Australian adults. This highlights the need to incorporate UQoL measures which are sensitive to the subclasses of obesity when evaluating obesity interventions.

Complexity of management and health outcomes in a prospective cohort study of 573 heart failure patients in Australia : does more equal less?

Aims and objectives : To compare the efficacy of chronic heart failure management programmes (CHF-MPs) according to a scoring algorithm used to quantify the level of applied interventions–the Heart Failure Intervention Score (HF-IS).

Background : The overall efficacy of heart failure programmes has been proven in several meta-analyses. However, the debate continues as to which components are essential in a heart failure programme to improve patient outcomes.

Design : Prospective cohort study of patients participating in heart failure programmes.

Method : Forty-eight of 62 (77%) programmes in Australia participating in a national register of CHF-MPs were evaluated using the HF-IS: derived from a summed and weighted score of each intervention applied by the CHF-MP (27 interventions overall). The CHF-MPs were prospectively categorised as relatively low (HF-IS < 190 – n = 39 programmes & 407 patients) or high (HF-IS ≥ 190 – n = 9 programmes & 166 patients) in complexity. Six-month morbidity and mortality rates in 573 consecutively recruited patients with systolic dysfunction and in New York Heart Association Class II–IV were prospectively examined.

Results : Patients exposed to CHF-MPs with a high HF-IS had a lower rate of unplanned, all-cause hospitalisation (n = 24, 14% vs. n = 102, 25%) compared with CHF-MPs with a low HF-IS within six months. On an adjusted basis, CHF-MPs with a high HF-IS were associated with a reduced risk of unplanned hospitalisation and/or death within six months and remained event-free longer.

Conclusion : High complexity CHF-MPs applying more evidence-based interventions are associated with a higher event-free survival over six months.

Relevance to clinical practice : The HF-IS is an easy-to-use evidence-based tool to assist programme coordinators to improve the quality of their heart failure programme which may also improve patient outcomes.

Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection.

Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Guérin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA257–264 failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c+ dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.

Trends in body mass index according to educational attainment for urban Australian adults between 1980 and 2007

BackgroundWe have previously demonstrated that between the years 1980 and 2000, the mean body mass index (BMI) of the urban Australian population increased, with greater increases observed with increasing BMI. The current study aimed to quantify trends over time in BMI according to education between 1980 and 2007.MethodsWe compared data from the 1980, 1983 and 1989 National Heart Foundation Risk Factor Prevalence Studies, 1995 National Nutrition Survey, 2000 Australian Diabetes, Obesity and Lifestyle Study and the 2007 National Health Survey. For survey comparability, analyses were restricted to urban Australian residents aged 25-64 years. BMI was calculated from measured height and weight. The education variable was dichotomised at completion of secondary school. Four age-standardised BMI indicators were compared over time by sex and education: mean BMI, mean BMI of the top five percent of the BMI distribution, prevalence of obesity (BMI⩾30 kg/m(2)), prevalence of class II(+) obesity (BMI⩾35 kg/m(2)).ResultsBetween 1980 and 2007, the mean BMI among men increased by 2.5 kg/m(2) and 1.7 kg/m(2) for those with low and high education levels, respectively, corresponding to increases in obesity prevalence of 20(from 12% to 32%) and 11(10% to 21%) %-points. Among women mean BMI increased by 2.9 kg/m(2) and 2.4 kg/m(2) for those with low and high education levels respectively, corresponding to increases in obesity prevalence of 16(12% to 28%) and 12(7% to 19%) %-points. The prevalence of class II(+) obesity among men increased by 9(1% to 10%) and 4(1% to 5%) %-points for those with low and high education levels, and among women increased by 8(4% to 12%) and 4(2% to 6%) %-points. Absolute and relative differences between education groups generally increased over time.ConclusionsEducational differences in BMI have persisted among urban Australian adults since 1980 without improvement. Obesity prevention policies will need to be effective in those with greatest socio-economic disadvantage if we are to equitably and effectively address the population burden of obesity and its corollaries.International Journal of Obesity accepted article preview online, 16 March 2015. doi:10.1038/ijo.2015.27.