The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.

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The adipose organ at a glance

Controversies and evolving new mechanisms in subarachnoid hemorrhage.

The increase of extracellular heme is a hallmark of hemolysis or extensive cell damage. Heme has prooxidant, cytotoxic, and inflammatory effects, playing a central role in the pathogenesis of malaria, sepsis, and sickle cell disease. However, the mechanisms by which heme is sensed by innate immune cells contributing to these diseases are not fully characterized. We found that heme, but not porphyrins without iron, activated LPS-primed macrophages promoting the processing of IL-1β dependent on nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3). The activation of NLRP3 by heme required spleen tyrosine kinase, NADPH oxidase-2, mitochondrial reactive oxygen species, and K+ efflux, whereas it was independent of heme internalization, lysosomal damage, ATP release, the purinergic receptor P2X7, and cell death. Importantly, our results indicated the participation of macrophages, NLRP3 inflammasome components, and IL-1R in the lethality caused by sterile hemolysis. Thus, understanding the molecular pathways affected by heme in innate immune cells might prove useful to identify new therapeutic targets for diseases that have heme release.

https://www.pnas.org/content/pnas/111/39/E4110.full.pdf

Hemolysis-induced lethality involves inflammasome activation by heme

Spontaneous intracerebral haemorrhage (ICH) is a particularly severe type of stroke for which no specific treatment has been established yet. Although preclinical models of ICH have substantial methodological limitations, important insight into the pathophysiology has been gained. Mounting evidence suggests an important contribution of inflammatory mechanisms to brain damage and potentially repair. Neuroinflammation evoked by intracerebral blood involves the activation of resident microglia, the infiltration of systemic immune cells and the production of cytokines, chemokines extracellular proteases and reactive oxygen species. Previous studies focused on innate immunity including microglia, monocytes and granulocytes. More recently, the role of adaptive immune cells has received increasing attention. Little is currently known about the interactions among different immune cell populations in the setting of ICH. Nevertheless, immunomodulatory strategies are already being explored in ICH. To improve the chances of translation from preclinical models to patients, a better characterization of the neuroinflammation in patients is desirable.

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Neuroinflammation after intracerebral hemorrhage.

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake More than 50 years ago, Otto G Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy" However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake This formulation has implications for understanding weight regulation and the management of obesity

Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

Subarachnoid haemorrhage (SAH) is a major contributor to the burden of stroke on society. Treatment options are limited and animal models of SAH do not always mimic key pathophysiological hallmarks of the disease, thus hindering development of new therapeutics. Inflammation is strongly associated with brain injury after SAH in animals and patients, and inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1) represents a possible therapeutic target. Here we report that a rupture of the middle cerebral artery in the rat produces heterogeneous infarct patterns similar to those observed in human SAH. Administration of the IL-1 receptor antagonist (IL-1Ra) reduced blood-brain barrier breakdown, and the extent of breakdown correlated with brain injury. After SAH, haem oxygenase-1 (HO-1) was strongly expressed around the bleed site and in the cortex and striatum, indicating the presence of free haem, a breakdown product of haemoglobin. HO-1 expression was also found in the same regions as microglial/macrophage expression of IL-1α. The direct effect of haem on IL-1α expression was confirmed in vitro using organotypic slice culture (OSC). Haem-induced cell death was dependent on IL-1 signalling, with IL-1Ra completely blocking cellular injury. Furthermore, stimulation of mouse primary mixed glial cells with haem induced the release of IL-1α, but not IL-1β. Thus, we suggest that haem, released from lysed red blood cells (RBCs) in the subarachnoid space, acts as a danger-associated molecular pattern (DAMP) driving IL-1-dependent inflammation. These data provide new insights into inflammation after SAH-induced brain injury and suggest IL-1Ra as a candidate therapeutic for the disease.

Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology.

Patient and public involvement and engagement is an important and expected component of health-related research activity in the UK. Specifically within the health research sphere, public engagement (usually defined as raising awareness of research) and patient involvement (usually defined as actively involving people in research) have traditionally been seen as separate but have much to gain from working together towards a common goal of better health outcomes for all. This paper describes a unique approach taken by the Public Programmes Team: a small interdisciplinary team of public engagement specialists, with backgrounds in science, community development, public engagement and involvement, policy, ethics, communications, industry, museums and creative practice, embedded within translational research infrastructure and delivery in Manchester in the North West of England. We propose a new model of professional practice – a 'cycle' of engagement and involvement – innovating across the complementary fields of public engagement and patient involvement, and working inclusively and in partnership with people in health research. Further, our approach capitalises on strategic collaboration offering economies of scale and a joined up way of working. Our ambition is to boldly experiment, learn and reflect, responsibly and based on evidence and partnerships, using methods of engagement that address issues of social justice. Here, we report on preliminary case studies exemplifying the impact of our approach, and data relating to achievements and learning between April 2017 and March 2018. Informed by our findings, we propose that our approach has the potential to be replicated elsewhere. Our practice and the beginning of its evaluation lead us to believe that our way of working and model of professional practice – the ‘cycle’ of engagement and involvement – is effective in: addressing our vision of making health research relevant and inclusive for everyone; and embedding and joining up public involvement in a busy and fertile translational health research ecosystem.

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Innovating public engagement and patient involvement through strategic collaboration and practice

Background and objective Athletics is the leading cause of pediatric concussion, and depression is a major comorbidity associated with concussion in the pediatric population. Prior studies have described the risk of depression after concussion in high school-, collegiate-, and elite-level athletes, but there is scarce data on younger athletes. Interpretation of existing research on the association of depression with concussions in youth athletes is complicated by diverse study designs, varying measures of depression, differing timelines for symptom development, and a lack of control groups. Furthermore, limited research exists on sex-related differences in the development of depressive symptoms following sports-related concussions (SRC) in younger athletes. This study used the Seattle Pediatric Concussion Research Collaborative (SPCRC) Data Repository to compare depressive symptoms between youth athletes at one month post-SRC and non-concussed age-matched controls by using a standardized measure of depressive symptoms: the Patient Health Questionnaire-9 (PHQ-9). The secondary goal was to compare PHQ-9 scores between males and females for both concussed and non-concussed groups. Methods This study entailed a secondary analysis of data collected as part of the SPCRC Data Repository. We conducted a retrospective subgroup analysis of PHQ-9 scores at one month post-concussion for concussed youth athletes. We compared the PHQ9 scores of concussed youth athletes with PHQ-9 scores collected at the time of enrollment for non-concussed youth athletes. Results After random age-matching, a cohort of 266 patients (133 in the concussed group and 133 in the non-concussed control group) was included in the final analysis. The mean age was 13.8 years (range: 5-18 years). For the concussed group, a history of SRC was associated with a higher mean total PHQ-9 score at one month post-concussion compared with the control group at the time of enrollment (6.14 ±5.46 versus 1.53 ±1.81, respectively, p<0.0001). All nine subdomains of the PHQ-9 showed significantly higher scores in the concussion group compared with the control group (p<0.0001). Significantly higher scores were observed when comparing mean total PHQ-9 scores for male athletes in the concussion group with male athletes in the control group (7.03 ±5.72 versus 1.59 ±1.66, p<0.0001) and for female athletes in the concussion group compared with female controls (5.28 ±5.10 versus 1.49 ±1.92, p<0.0001). No significant differences were observed between sexes for total PHQ-9 scores or PHQ-9 subscores. Conclusion At one month post concussion, youth with SRC demonstrated higher levels of depressive symptoms as measured by PHQ-9 compared with age-matched typically developing controls. No significant differences were identified in total PHQ-9 scores and subscores between male and female participants for either the concussion or control group. This study suggests that clinicians need to be vigilant and monitor for symptoms of depression in young athletes for at least one month post-concussion.

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A Comparative Analysis of Depressive Symptoms Following Sports-Related Concussion in Youth Athletes Versus Their Age-Matched Non-concussed Counterparts

Emily Robinson

Papers

Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology.

Innovating public engagement and patient involvement through strategic collaboration and practice

A Comparative Analysis of Depressive Symptoms Following Sports-Related Concussion in Youth Athletes Versus Their Age-Matched Non-concussed Counterparts