Preliminary characterisation of the neuropeptide melanin concentrating hormone in humans

Melanin concentrating hormone (MCH) is an orexigenic neuropeptide expressed centrally in the zona incerta and lateral hypothalamus. Evidence from rodent studies implicates hypothalamic MCH in the modulation of varied and diverse physiological functions most notably in energy homeostasis but also emerging as a candidate mediator in reproductive activities. These two aspects of normal physiology are intimately related though the pathways through which they integrate are only just being explored. Currently little is known about the actions, sources or targets of peripheral or circulating MCH. This study is the first to describe normal physiological concentrations of circulating MCH in humans. Particular emphasis has been devoted to aspects which might further understanding of the dual roles of circulating MCH in energy balance and reproductive function. A primary objective was to develop and validate a tool with which to quantifiably measure circulating MCH concentrations since previous work in this area has failed to reconcile this objective. Following the successful validation of a radioimmunoassay (RIA), three studies were undertaken with human subjects drawn from 3 distinct sample populations. The chief objectives were 1) to detect changes in circulating MCH post-prandial in association with other metabolic markers of energy homeostasis; 2) to determine associations between circulating MCH concentrations and resting metabolic rate (RMR); and 3) to detect changes in circulating MCH concentrations during the menstrual cycle. The results indicate that circulating MCH concentrations may be involved in glucose homeostasis since there were associations between the post-prandial MCH and the post-prandial insulin response. Circulating MCH may also convey information regarding the nutritional status of the individual, though this appears to be influenced by a combination of gender and adiposity status. Circulating MCH concentrations remained stable over the course of the menstrual cycle and were not strongly aligned to RMR. Whilst there were emergent patterns and trends there were also inconsistencies between the sample populations. This initial characterisation may be constructive for future exploration of the physiological relevance of circulating MCH in humans

Preliminary characterisation of the neuropeptide melanin concentrating hormone in humans

Melanin concentrating hormone (MCH) is an orexigenic neuropeptide expressed centrally in the zona incerta and lateral hypothalamus. Evidence from rodent studies implicates hypothalamic MCH in the modulation of varied and diverse physiological functions most notably in energy homeostasis but also emerging as a candidate mediator in reproductive activities. These two aspects of normal physiology are intimately related though the pathways through which they integrate are only just being explored. Currently little is known about the actions, sources or targets of peripheral or circulating MCH. This study is the first to describe normal physiological concentrations of circulating MCH in humans. Particular emphasis has been devoted to aspects which might further understanding of the dual roles of circulating MCH in energy balance and reproductive function. A primary objective was to develop and validate a tool with which to quantifiably measure circulating MCH concentrations since previous work in this area has failed to reconcile this objective. Following the successful validation of a radioimmunoassay (RIA), three studies were undertaken with human subjects drawn from 3 distinct sample populations. The chief objectives were 1) to detect changes in circulating MCH post-prandial in association with other metabolic markers of energy homeostasis; 2) to determine associations between circulating MCH concentrations and resting metabolic rate (RMR); and 3) to detect changes in circulating MCH concentrations during the menstrual cycle. The results indicate that circulating MCH concentrations may be involved in glucose homeostasis since there were associations between the post-prandial MCH and the post-prandial insulin response. Circulating MCH may also convey information regarding the nutritional status of the individual, though this appears to be influenced by a combination of gender and adiposity status. Circulating MCH concentrations remained stable over the course of the menstrual cycle and were not strongly aligned to RMR. Whilst there were emergent patterns and trends there were also inconsistencies between the sample populations. This initial characterisation may be constructive for future exploration of the physiological relevance of circulating MCH in humans.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Educational engagement practices of Tongan parents in relation to their children's learning

This study explores the parental engagement of Tongan parents in relation to their children’s learning and designs an engagement framework to enhance this engagement. Bronfenbrenner’s (1979) ecological systems theory framework was employed to conceptualise and inform the analysis of parental engagement of Tongan parents in this research. Talaloto, a new Pacific research methodology which I developed for use in this study, was utilised for data collection from Tongan parents, as a way of capturing their authentic voices, grounded within their culture. Talaloto provides a space for personal lived experiences to be told. Focus group interviews were used for gathering data from teachers and students. Initial data collection motivated me to develop and implement an intervention to enhance parental engagement practices, for a sample of Tongan parents, students, and teachers, associated with a local primary school. The findings showed that parental engagement is an holistic process, requiring collaboration between home, school, and the wider community to enable both participation and interaction. Recognition of and valuing home funds of knowledge as well as the implementation of home visits by teachers, were found to be significant contributors to transforming relationships and lifting student achievement. The intentional creation of an Engagement Broker role for the purposes of the intervention demonstrated the importance of such a role in providing guidance to all participants as they navigated differing contexts and new roles and relationships. A key outcome of this study was the development of the ‘Kato Alu ‘framework, where a cultural metaphor is used to conceptualise and contextualise the understanding and use of parental engagement practices by Tongan parents in their children’s learning. I used the four stages of crafting the Kato Alu: Tokonaki (preparation), Lalanga (weaving), Teuteu’i (decoration) and Foaki (presentation), to symbolise the four steps for guiding the parental engagement process. The hope is that this framework may be applied in other Pacific settings and can be adapted for broader use

A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India

Purpose. Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. Method. This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. Results. Patients in the control group (n = 15) had significantly decreased body weight (P = .003), mid–upper-arm circumference (P = .002), and body fat (P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat (P = .002) was observed; moreover, patients reported a significant improvement in fatigue (P = .002) and appetite scores (P = .006) under quality-of-life domains at the end of intervention. Conclusions. Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients

The effect of the visual exercise environment on the response to psychological stress: a pilot study

Background: Performing physical activity whilst exposed to nature can improve health. However, there is little evidence of its impact on stress outcomes. The aim of this study was to examine the influence of the visual exercise environment on the response to a psychosocial stressor. Methods: Eighteen participants were randomised to one of three conditions: i. control; ii. Nature or; iii. Built condition. Participants exercised for 30min on a treadmill at 50% of their VO2max whilst viewing a video of either a natural or built environment or a blank screen. Following the exercise, participants completed the Trier Social Stress Test (TSST), a standardised laboratory stressor. Salivary samples were collected before, during and after the TSST to calculate cortisol reactivity and recovery. Results: One-way ANOVA revealed a significant effect of viewing condition on cortisol reactivity [F (2, 11) = 4.686, p = .034; n2p= .460]; with significantly lower reactivity in the built compared to the nature condition (p = .027, d=1.73). There was no effect of condition on cortisol recovery (P>0.05; n2p= .257). Conclusions: In the context of the adverse health impact of lower (i.e. blunted) cortisol responding, these findings could indicate a negative impact of the built environment on stress responses

Melanin-concentrating hormone in peripheral circulation in the human

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5–1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5–55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role

High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals

Context Insulin resistance in skeletal muscle contributes to whole body hyperglycaemia and the secondary complications associated with type 2 diabetes. Inositol hexakisphosphate kinase-1 (IP6K1) may inhibit insulin-stimulated glucose transport in this tissue type. Objective Muscle and plasma IP6K1 were correlated with two-compartment models of glucose control in insulin-resistant hyperinsulimic individuals. Muscle IP6K1 was also compared following two different exercise trials. Methods Nine pre-diabetic [HbA1c; 6.1 (0.2) %)] were recruited to take part in a resting control, a continuous exercise (90% of lactate threshold) and a high-intensity exercise trial (6 x 30 sec sprints). Muscle biopsies were drawn pre- and post each 60-minute trial. A labeled ([6,62H2]glucose) intravenous glucose tolerance test (IVGTT) was performed immediately after the second muscle sample. Results Fasting muscle IP6K1 content did not correlate with SI2* (P = 0.961). High-intensity exercise reduced IP6K1 muscle protein and mRNA expression (P = 0.001). There was no effect on protein IP6K1 content following continuous exercise. Akt308 phosphorylation of was significantly greater following high-intensity exercise. Intermittent exercise reduced hepatic glucose production (HGP) following the same trial. The same intervention also improved SI2* and this was significantly greater compared to the continuous exercise improvements. Our in vitro experiment demonstrated that the chemical inhibition of IP6K1 increased insulin signaling in C2C12 myotubes. Conclusions The in vivo and in vitro approaches used in the current study suggest that a decrease in muscle IP6K1 may be linked to whole body improvements in SI2*. In addition, high-intensity exercise reduces HPG in insulin-resistant individuals

Melanin concentrating hormone in peripheral circulation in the human

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role

The evolution of neuropeptide signalling: insights from echinoderms

This work was supported by Leverhulme Trust grant RGP-2013-351 and BBSRC grant BB/M001644/1 (awarded to M.R.E.). Dean Semmens has a BSc in Molecular and Cellular Biology (University of Bath, 2011), a PhD in Neurobiology (Queen Mary University of London, 2015) and is a Leverhulme Trust-funded Postdoctoral Fellow. Maurice Elphick studied at Royal Holloway University of London (BSc Biology, 1988; PhD Neurobiology, 1991) and became Professor of Physiology and Neuroscience at Queen Mary University of London in 2004