Uncovering a role for micro-RNAs in sleep homeostasis and energy metabolism

Micro-RNAs (miRNAs) are key, post-transcriptional regulators of gene expression and have been implicated in almost every cellular process investigated thus far. However, their role in sleep, in particular the homeostatic aspect of sleep control, has received little attention. We here assessed the effects of sleep deprivation on the brain miRNA transcriptome in the mouse. Sleep deprivation affected miRNA expression in a brain-region specific manner. The forebrain expression of the miRNA miR-709 was affected the most and in situ analyses confirmed its robust increase throughout the brain, especially in the cerebral cortex and the hippocampus. The hippocampus was a major target of the sleep deprivation affecting 37 miRNAs compared to 52 in the whole forebrain. Moreover, independent from the sleep deprivation condition, miRNA expression was highly region-specific with 45% of all expressed miRNAs showing higher expression in hippocampus and 55% in cortex. Next we demonstrated that down-regulation of miRNAs in Com/c2o-expressing neurons of adult mice, through a conditional and inducible Dicer knockout mice model (cKO), results in an altered homeostatic response after sleep deprivation eight weeks following the tamoxifen-induced recombination. Dicer cKO mice showed a larger increase in the electro-encephalographic (EEG) marker of sleep pressure, EEG delta power, and a reduced Rapid Eye Movement sleep rebound, compared to controls, highlighting a functional role of miRNAs in sleep homeostasis. Beside a sleep phenotype, Dicer cKO mice developed an unexpected, severe obesity phenotype associated with hyperphagia and altered metabolism. Even more surprisingly, after reaching maximum body weight 5 weeks after tamoxifen injection, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of processes involved in reversing obesity. Moreover, our study identified the cortex as a brain area important for body weight homeostasis. Together, these observations strongly suggest a role for miRNAs in the maintenance of homeostatic processes in the mouse, and support the hypothesis of a tight relationship between sleep and metabolism at a molecular - Les micro-ARNS (miARNs) sont des régulateurs post-transcriptionnels de l'expression des gènes, impliqués dans la quasi-totalité des processus cellulaires. Cependant, leur rôle dans la régulation du sommeil, et en particulier dans le maintien de l'homéostasie du sommeil, n'a reçu que très peu d'attention jusqu'à présent. Dans cette étude, nous avons étudié les conséquences d'une privation de sommeil sur l'expression cérébrale des miARNs chez la souris, et observé des changements dans l'expression de nombreux miARNs. Dans le cerveau antérieur, miR-709 est le miARN le plus affecté par la perte de sommeil, en particulier dans le cortex cérébral et l'hippocampe. L'hippocampe est la région la plus touchée avec 37 miARNs changés comparés à 52 dans le cerveau entier. Par ailleurs, indépendamment de la privation de sommeil, certains miARNs sont spécifiquement enrichis dans certaines aires cérébrales, 45% des miARNs étant surexprimés dans l'hippocampe contre 55% dans le cortex. Dans une seconde étude, nous avons observé que la délétion de DICER, enzyme essentielle à la biosynthèse des miARNs, et la perte subséquente des miARNs dans les neurones exprimant la protéine CAMK2a altère la réponse homéostatique à une privation de sommeil, 8 semaines après l'induction de la recombinaison génétique par le tamoxifen. Les souris sans Dicer (cKO) ont une plus large augmentation de l'EEG delta power, le principal marqueur électro-encéphalographique du besoin de sommeil, comparée aux contrôles, ainsi qu'un rebond en sommeil paradoxal plus petit. De façon surprenante, les souris Dicer cKO développent une obésité rapide, sévère et transitoire, associée à de l'hyperphagie et une altération de leur métabolisme énergétique. Après avoir atteint un pic maximal d'obésité, les souris cKO entrent spontanément dans une période de perte de poids rapide. L'analyse du transcriptome cérébral des souris obèses nous a permis d'identifier des voies associées à l'obésité (leptine, somatostatine et nemo-like kinase), et à la prise alimentaire (Pmch, Neurotensin), tandis que celui des souris post-obèses a révélé un groupe de gènes liés à la plasticité synaptique. Au-delà des nombreux modèles d'obésité existant chez la souris, notre étude présente un modèle unique permettant d'étudier les mécanismes sous-jacent la perte de poids. De plus, nous avons mis en évidence un rôle important du cortex cérébral dans le maintien de la balance énergétique. En conclusion, toutes ces observations soutiennent l'idée que les miARNs sont des régulateurs cruciaux dans le maintien des processus homéostatiques et confortent l'hypothèse d'une étroite relation moléculaire entre le sommeil et le métabolisme.

Framework for Preventing and Addressing Overweight and Obesity in Northern Ireland 2012-2022: A Fitter Future for All (PDF 1MB)

A Framework for Preventing and Addressing Overweight and Obesity in NI 2012-2022 This Framework aims to “empower the population of Northern Ireland to make healthy choices, reduce the risk of overweight and obesity related diseases and improve health and wellbeing, by creating an environment that supports and promotes a physically active lifestyle and a healthy diet”. In addition, the following overarching targets have been set: Adults • To reduce the level of obesity by 4% and overweight and obesity by 3% by 2022. Children • A 3% reduction of obesity and 2% reduction of overweight and obesity by 2022åÊThe target is in two parts; the proportion that are obese and the proportion that are overweight and obese. Prevention is typically taken forward through action to address two main areas – improving diet and nutrition, and increasing participation in physical activity. Acknowledging this, two overarching objectives for the Framework have been set: to increase the percentage of people eating a healthy, nutritionally balanced diet; and to increase the percentage of the population meeting the CMO guidelines on physical activity.

Characterization of constitutive and putative differentially expressed mRNAs by means of expressed sequence tags, differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR from the sand fly vector Lutzomyia longipalpis

Molecular studies of insect disease vectors are of paramount importance for understanding parasite-vector relationship. Advances in this area have led to important findings regarding changes in vectors' physiology upon blood feeding and parasite infection. Mechanisms for interfering with the vectorial capacity of insects responsible for the transmission of diseases such as malaria, Chagas disease and dengue fever are being devised with the ultimate goal of developing transgenic insects. A primary necessity for this goal is information on gene expression and control in the target insect. Our group is investigating molecular aspects of the interaction between Leishmania parasites and Lutzomyia sand flies. As an initial step in our studies we have used random sequencing of cDNA clones from two expression libraries made from head/thorax and abdomen of sugar fed L. longipalpis for the identification of expressed sequence tags (EST). We applied differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR to characterize differentially expressed mRNA from sugar and blood fed insects, and, in one case, from a L. (V.) braziliensis-infected L. longipalpis. We identified 37 cDNAs that have shown homology to known sequences from GeneBank. Of these, 32 cDNAs code for constitutive proteins such as zinc finger protein, glutamine synthetase, G binding protein, ubiquitin conjugating enzyme. Three are putative differentially expressed cDNAs from blood fed and Leishmania-infected midgut, a chitinase, a V-ATPase and a MAP kinase. Finally, two sequences are homologous to Drosophila melanogaster gene products recently discovered through the Drosophila genome initiative.

Healthy child, healthy future: speech and language therapy for children

This resource is designed to reinforce a collaborative approach between speech and language therapists, referrers and parents in the identification and management of children with developmental speech and language and communication needs (including children with feeding and/or swallowing difficulties). It includes a comprehensive key skills section, which provides details on the communication-related skills a child should have acquired at each stage in his/her early years development. It also includes specific criteria and guidelines for referral, should there be concern about whether the child has a significant problem. The resource provides additional guidance on: • communication and child play; • speech sound development; • dummies; • stammering; • dysphonia; • bilingualism; • feeding and swallowing difficulties. Lists of supplementary leaflets, handouts and websites, as well as a bibliography, are also included.

Young People and Food: Adolescent Dietary Beliefs and Understandings

This research provides fresh insight into the dichotomy between young people's knowledge of food safety and nutrition, and their behaviour.

National Health and Lifestyle Surveys

Results of the National Health and Lifestyle Surveys: SLaN [Survey of Lifestyle, Attitudes and Nutrition] and HBSC [Health Behaviour in School-Aged Children] Two baseline surveys of health related behaviours among adults and schoolgoing young people were carried out across the Republic of Ireland in 1998 and again in 2002. The main aims of these surveys are to: - Produce reliable data of a representative cross-section of the Irish population in order to inform the Department of Health and Children's policy and programme planning. - Maintain a survey protocol which will enable lifestyle factors to be remeasured so that trends can be identified and changes monitored to assist national and regional setting of priorities in health promotion activities. In keeping with the health and lifestyle surveillance system of many European countries a number of related factors were measured in both surveys. These include general health, smoking, use of alcohol and other substances, food and nutrition, exercise and accidents. This work was commissioned by the Health Promotion Unit, Department of Health and Children and carried out at the Centre for Health Promotion Studies, National University of Ireland, Galway.This resource was contributed by The National Documentation Centre on Drug Use.

National Health and Lifestyle Surveys. Regional Summary Report (2003)

Two baseline surveys of health related behaviours among adults and school-going young people were carried out across the Republic of Ireland in 1998 and again in 2002. The main aims of these surveys are to: - Produce reliable data of a nationally representative cross-section of the Irish population in order to inform the Department of health and Children's policy and programme planning. - Maintain a survey protocol which will enable lifestyle factors to be re-measured so that trends can be identified and changes monitored to assist national and regional setting of priorities in health promotion activities. This report focuses on these two cross-sectional studies, SLaN (Survey of Lifestyles, Attitudes and Nutrition) adults aged 18+ years and HBSC (health Behaviour in School-aged Children) school-going children aged 10-17 years. In keeping with the health and lifestyle surveillance system of many European countries a number of related factors were measured in both surveys. These include general health, smoking, use of alcohol and other substances, food and nutrition, exercise and accidents. This report presents the findings for the same topics at a regional level with some demographic analysis. It must be noted that the aim of the survey was to establish patterns in health and lifestyle at a national level. The significance therefore of findings at the regional level is to identify potential variations that may merit further investigation. This work was commissioned by the health Promotion Unit, Department of health and Children and carried out at the Centre for health Promotion Studies, national University of Ireland, Galway, and at the Department of Public health Medicine and Epidemiology, Woodview House, Belfield, national University of Ireland, Dublin.This resource was contributed by The National Documentation Centre on Drug Use.

Hungry for Change: Social Exclusion, Food Poverty and Homelessness in Dublin

This study investigates the impact of poverty and social exclusion on the food, diet and nutrition of people out-of-home in Dublin. The research involved a food frequency survey carried out with 75 people out of home, qualitative interviews with 12 individuals as well as a self-completion questionnaire administered to 18 food service providers in Dublin city. One of the main findings from the study was that the extent and experience of food poverty among homeless people was not only conditioned by income inadequacy and other socio-economic and cultural determinants, but particularly, by access to accommodation, as well as the quality of that accommodation. The report makes a number of practice and policy recommendations to tackle food poverty and homelessness. The qualitative approaches to food poverty employed for use with this sample of people out-of-home aimed to deal in depth with issues around food consumption. Through drawing a sub-sample from those who participated in the survey research (a process of recapture), the authors sought to expand on the survey questionnaire information on food issues. The themes for the Focus Group Discussions (FGDs) emerged from the analysis of the survey questionnaires and 4 key thematic areas were selected. i) Access to cooking, preparation and storage facilities ii) Access, choice and constraints in food purchase and consumption iii) Access to information about healthy diet, food preparation and storage iv) Expectations, cultures, values and choice concerning eating The qualitative aspect of the research enquiry eventually generated one FGD and seven semi-structured interviews representing the views of a total of 12 persons all of whom had completed the initial survey questionnaire.This resource was contributed by The National Documentation Centre on Drug Use.

Food and Health Project Longford/Westmeath

The Food and Health Project offers practical healthy eating and lifestyle courses to groups cooking on a lower income. Courses offered include: C/O Athlone Community Taskforce Ball Alley Lane Athlone Westmeath HSE and community group Initiative Type Nutrition Education and Training Programmes Location Longford Westmeath Funding HSE and community group Partner Agencies HSE

Journeyman Programme Kitchen and Garden

A new community kitchen and community garden are nearing the end of development. The area around the kitchen is designated for the community garden and is being developed this year. Running in conjunction with a school leavers programme, the garden will be an inclusive area for young people with disabilities. The community kitchen is expected to be used by the refugee centre and also local schools. Private fundraising and County Council grants Initiative Type Community Food Centres Community Food Growing Projects Location Tipperary Funding Private fundraising and County Council grants

Food and Health Project

Provision of community based Healthy Food Made Easy, Cool Dude and related courses. Based at Birchgrove Community Centre, Birchgrove, Portlaoise. HSE Initiative Type Nutrition Education and Training Programmes Location Laois Offaly Funding HSE Partner Agencies HSE Health Promotion

Kilkenny Allotments and Community Gardens Association

Our aim is to provide affordable sites for growing food across the city of Kilkenny and to provide education to families, individuals and community groups around growing food. Kilkenny Local Authorities Initiative Type Community Food Growing Projects Location Kilkenny Funding Kilkenny Local Authorities Partner Agencies Carlow Kilkenny Leader Partnership Future Proof Kilkenny GIY Kilkenny Local Authorities

Colin Glen Community Gardens and Allotments

This project forms part of Groundwork NIâ?Ts Sharing our Space programme, which aims to transform derelict, unwelcoming & underused sites into shared facilities. Peace III, SEUPB Initiative Type Community Food Growing Projects Location Antrim Funding Peace III, SEUPB Partner Agencies Colin Neighbourhood Partnership

General and Abdominal Adiposity and Risk of Death in Europe

Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. This study examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). A Cox regression analysis was used, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height.

Total energy expenditure and patterns of activity in 8-10-year-old obese and nonobese children.

Total energy expenditure (TEE) and patterns of activity were measured by means of a heart rate (HR)-monitoring method in a group of 8-10-year-old children including 13 obese children (weight, 46 +/- 10 kg; fat mass: 32 +/- 9%) and 16 nonobese children (weight, 31 +/- 5 kg; fat mass, 18 +/- 5%). Time for sleeping was not statistically different in the two groups of children (596 +/- 33 vs. 582 +/- 43 min; p = NS). Obese children spent more time doing sedentary activities (400 +/- 129 vs. 295 +/- 127 min; p < 0.05) and less time in nonsedentary activities (449 +/- 126 vs. 563 +/- 135 min; p < 0.05) than nonobese children. Time spent in moderate or vigorous activity-i.e., time spent at a HR between 50% of the maximal O2 uptake (peak VO2) and 70% peak VO2 (moderate) and at a HR > or = 70% peak VO2 (vigorous)-was not statistically different in obese and nonobese children (88 +/- 69 vs. 52 +/- 35 min and 20 +/- 21 vs. 16 +/- 13 min, respectively; p = NS). TEE was significantly higher in the obese group than in the nonobese group (9.46 +/- 1.40 vs. 7.51 +/- 1.67 MJ/day; p < 0.01). The energy expenditure for physical activity (plus thermogenesis) was significantly higher in the obese children (3.98 +/- 1.30 vs. 2.94 +/- 1.39 MJ/day; p < 0.05). The proportion of TEE daily devoted to physical activity (plus thermogenesis) was not significantly different in the two groups, as shown by the ratio between TEE and the postabsorptive metabolic rate (PMR): 1.72 +/- 0.25 obese vs 1.61 +/- 0.28 non-obese. In conclusion, in free-living conditions obese children have a higher TEE than do nonobese children, despite the greater time devoted to sedentary activities. The higher energy cost to perform weight-bearing activities as well as the higher absolute PMR of obese children help explain this apparent paradox.