GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Gαi. Here, we agree with a contradictory report in finding ...no expression of GPR41 in murine adipose tissue. Nevertheless, in the presence of adenosine deaminase to minimise Gαi signalling via the adenosine A1 receptor, SCFA stimulated leptin secretion by adipocytes from wild-type but not GPR41 knockout mice. Expression of GPR43 was reduced in GPR41 knockout mice. Acetate but not butyrate stimulated leptin secretion in wild-type mesenteric adipocytes, consistent with mediation of the response by GPR43 rather than GPR41. Pertussis toxin prevented stimulation of leptin secretion by propionate in epididymal adipocytes, implicating Gαi signalling mediated by GPR43 in SCFA-stimulated leptin secretion.
This paper uses conceptual resources drawn from psychosocial process thinking (Brown & Reavey, 2015; Brown & Stenner, 2009; Stenner, 2017) and from G.H. Mead in particular, to contribute to an ...emerging body of work on the experiences of adult women with ADHD (Horton‐Salway & Davies, 2018; Quinn & Madhoo, 2014; Singh, 2002; Waite & Ivey, 2009). It has a particular focus on how ADHD features in the construction of women's identities and life‐stories and it draws upon findings from a qualitative investigation of adult women diagnosed or self‐diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). A theoretically informed ‘thematic decomposition’ of 16 depth interviews reveals how complex processes of identity transformation are mediated by the social category of ADHD. Through this process, troubled pasts are reconstructed from the perspective of an ‘emergent’ identity that offers participants the potential for a more enabling and positive future.
Epidemiological data indicate that an adverse maternal environment during pregnancy predisposes offspring to metabolic syndrome with increased obesity, and type 2 diabetes. The mechanisms are still ...unclear although epigenetic modifications are implicated and the hypothalamus is a likely target. We hypothesized that maternal undernutrition (UN) around conception in sheep would lead to epigenetic changes in hypothalamic neurons regulating energy balance in the offspring, up to 5 years after the maternal insult. We found striking evidence of decreased glucocorticoid receptor (GR) promoter methylation, decreased histone lysine 27 trimethylation, and increased histone H3 lysine 9 acetylation in hypothalami from male and female adult offspring of UN mothers. These findings are entirely compatible with the increased GR mRNA and protein observed in the hypothalami. The increased GR predicted the decreased hypothalamic proopiomelanocortin expression and increased obesity that we observed in the 5-year-old adult males. The epigenetic and expression changes in GR were specific to the hypothalamus. Hippocampal GR mRNA and protein were decreased in UN offspring, whereas pituitary GR was altered in a sex-specific manner. In peripheral polymorphonuclear leukocytes there were no changes in GR methylation or protein, indicating that this epigenetic analysis did not predict changes in the brain. Overall, these results suggest that moderate changes in maternal nutrition, around the time of conception, signal life-long and tissue-specific epigenetic alterations in a key gene regulating energy balance in the hypothalamus.
Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but ...could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.
This article explores the perspectives of Pakistani-heritage Muslim young people on their educational progress, against a background where Muslim students are monitored for their vulnerability to ...radicalisation. The literature offers competing explanations for the persistent inequalities in attainment among different minority-ethnic groups, but the voices of pupils themselves are seldom heard. In this study, young people offer their own explanations of distinctive aspects within the local attainment data, which run counter to national trends. The principal sources of data are extended discussions with 36 Pakistani-heritage young people, and a survey conducted by some of the young people among 165 of their peers. Analysed through a Bourdieuian lens, the findings indicate that these Muslim young people are motivated by a strong sense of habitus and religious identity that transcends the divisions of social class. Further, they are actively engaged in habitus transformation, which drives their educational aspirations but involves personal cost, dilemmas and constraints.
Glucocorticoids (GCs) are widely prescribed medications that are well recognized to cause adverse metabolic effects including hyperphagia, obesity, and hyperglycemia. These effects have been ...recapitulated in a murine model of GC excess, and we hypothesize that they are mediated, in part, through central mechanisms. This study aimed to identify genes in the hypothalamic arcuate nucleus (ARC) that are altered with GC treatment and evaluate their contribution to GC-induced metabolic abnormalities.
Corticosterone (Cort; 75 μg/ml) was administered in the drinking water to male C57Bl/6J mice for 2 days or 4 weeks. Phenotypic analysis of each group was undertaken and central and peripheral tissues were collected for biochemical and mRNA analyses. Arcuate nuclei were isolated by laser capture microdissection and tissue analyzed by RNA-seq.
RNA-seq analysis of ARC tissue from 4 week Cort treated mice revealed 21 upregulated and 22 downregulated genes at a time when mice had increased food intake, expansion of adipose tissue mass, and insulin resistance. In comparison, after 2 days Cort treatment, when the main phenotypic change was increased food intake, RNA-seq identified 30 upregulated and 16 downregulated genes. Within the genes altered at 2 days were a range of novel genes but also those known to be regulated by GCs, including Fkbp5, Mt2, Fam107a, as well as some involved in the control of energy balance, such as Agrp, Sepp1, Dio2, and Nmb. Of the candidate genes identified by RNA-seq, type-II iodothyronine deiodinase (Dio2) was chosen for further investigation as it was increased (2-fold) with Cort, and has been implicated in the control of energy balance via the modulation of hypothalamic thyroid hormone availability. Targeted knockdown of Dio2 in the MBH using AAV-mediated CRISPR-Cas9 produced a mild attenuation in GC-induced brown adipose tissue weight gain, as well as a 56% reduction in the GC-induced increase in Agrp. However, this conferred no protection from GC-induced hyperphagia, obesity, or hyperglycemia.
This study identified a comprehensive set of genes altered by GCs in the ARC and enabled the selection of key candidate genes. Targeted knockdown of hypothalamic Dio2 revealed that it did not mediate the chronic GC effects on hyperphagia and hyperglycemia.
•RNA-seq reveals multiple genes changed by Cort in the arcuate nucleus.•Corticosterone increases Dio2 expression in the mediobasal hypothalamus.•Dio2 increase associated with greater food intake after 2 day Cort.•CRISPR-Cas9 knockdown of Dio2 attenuates the Cort-induced increase in Agrp.•Elevated Dio2 does not drive the GC-induced adverse metabolic effects.
Drawing on her experience as a professional storyteller, in this book, Alison Davies show teachers how to develop storytelling skills as part of a new engaging approach to creative teaching and ...learning. Packed with hands on, practical advice, the book also includes a range of stories for teachers to use in different class situations. The stories are in an easy to learn format, with pointers and tips on how to tell them and how to involve the class. Topics covered include: - bullying - disabilities - computer games - friendship - greed There are also lots of lesson plans with ideas for starters, mains and plenary sessions, and tips on developing creativity and presentation of ideas in an engaging manner to suit any topic or situation across the curriculum. As well as giving the reader the opportunity to practice their new skills and giving them the confidence to develop their own stories, the activities help them to develop these skills in young people. The book is ideal for teachers, teaching assistants, youth club workers-anyone in a primary level setting who has the opportunity to develop storytelling as a creative and inspirational experience.
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