Project description:Alterations in endoplasmic reticulum (ER) homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (a-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic a-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective a-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress, and establish a-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D.

2015-06-18 | GSE62263 | GEO

Aeromonas phage MSh-2020a isolate:Environment

Project description:Aeromonas phage MSh-2020a isolate:Environment Genome sequencing

| PRJNA641255 | ENA

Reduced a-MSH underlies hypothalamic endoplasmic reticulum stress-induced hepatic gluconeogenesis

2015-06-18 | E-GEOD-62263 | biostudies-arrayexpress

Multicenter Study of Hydroxyurea (MSH)

Project description:Multicenter Study of Hydroxyurea (MSH)

| PRJNA701327 | ENA

Multicenter Study of Hydroxyurea (MSH)

Project description:Multicenter Study of Hydroxyurea (MSH)

| PRJNA701326 | ENA

Microarray analysis of the effects of ASP/MSH in melan-a melanocytes

Project description:We determined the gene expression profiles of murine melan-a melanocytes treated with ASP or alpha-MSH over a 4 days time course using genome-wide oligonucleotide microarrays. As expected, the gene expression patterns emphasized the opposing effects of the 2 ligands, and there were significant reductions in expression of numerous melanogenic proteins elicited by ASP, which correlates with its inhibition of pigmentation. However, ASP also unexpectidly modulated the expression of genes involved in various other cellular pathways, including glutathione synthesis and redox metabolism. Many genes up-regulated by ASP are involved in morphogenesis, cell adhesion and ECM-receptor interactions. Treatment with ASP or alpha-MSH was performed for 3 hr, 1 day, 2 days, 3 days and 4 days, in triplicate. Each biological replicate was submitted to a direct hybridization (treated/untreated samples) after coupling with Cy5 or Cy3 and to a reverse dye-swap, leading to 2 replicated hybridization for each biological sample. A total of 6 hybridized arrays was used for each of the 5 time points, for each drug.

2009-02-02 | E-GEOD-14089 | biostudies-arrayexpress

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