Necessity and sufficiency of leptin signaling in POMCARC neurons for HPA axis activity suppression during fasting-induced stress

• Grant number: 18/06871-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2018
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Rodrigo César Rorato
• Grantee: Taís Do Nascimento
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated research grant: 16/17968-6 - Hypothalamic neuronal circuitry and phenotypes involved in the coupling of hypothalamic-pituitary-adrenal axis activity to changes in the energy homeostasis, AP.JP

Abstract

It has been suggested that hypothalamic-pituitary-adrenal (HPA) axis hyperactivation could account for obesity and metabolic syndrome, since the end product of this axis, the glucocorticoid, has important adipogenic actions. Interestingly, it has also been suggested that the HPA axis activation is coupled to changes in peripheral energy stores. However, the neurocircuitry and the neuronal phenotypes involved in this coupling are unknown. Considering the high leptin receptor expression (LepR) in ARC neurons and the huge number of inputs that PVN neurons receive from the ARC, this study aims: 1) To determine the necessity and sufficiency of leptin signaling in POMC ARC neurons (POMCARC) to corticosterone secretion under metabolic challenge (fasting) using conditional gene edition using the Cre-LoxP system and 2) To investigate whether selective and specific neuronal activity manipulation of POMCARC using DREADD technology (Receptors Designed Exclusively Designed by Activated Drugs) can restore corticosterone plasma levels in fasted animals. Our study will permit us to identify the neuronal subsets and the neurocircuitry involved in the adrenal axis regulation during nutritional stress and may contribute to the recognition of new and specific therapeutic targets important to the treatment of disorders metabolic. (AU)