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

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Jordi Altirriba 

PROVIDER: E-GEOD-62263 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress