Effect of specific modulation of the activity of CRFPVN and AgRPARC neurons on the hypothalamus-pituitary-adrenal axis in diet-induced obese animals.

• Grant number: 23/12478-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Rodrigo César Rorato
• Grantee: Ana Beatriz de Assis Marçal
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The increased activity of neurons that produce and secrete corticotrophin-releasing factor (CRF), located in the paraventricular nucleus of the hypothalamus (PVN) and, consequently, the activation of the hypothalamic-pituitary-adrenal (HPA) axis, is observed in response to stress induced by food deprivation. At least in part, the increased activity of the HPA axis during fasting is associated with decreased plasma concentrations of leptin. The leptin receptors (Lepr) are not expressed in CRFPVN neurons, indicating that leptin's effects on the activity of the HPA axis are indirect. Indeed, Leprs are expressed in neurons that synthesize the agouti-related peptide (AgRP) in the arcuate nucleus (ARC), and results from our group have demonstrated that AgRPARC neuronal activation is important to the HPA axis activation during fasting. Interestingly, there are studies showing that animals with diet-induced obesity show a significant increase in plasma corticosterone concentrations and are hyperleptinemic, but are resistant to leptin actions, including its effects on AgRP neuronal activity. In addition, these animals have a reorganization of ARC neuronal projections sensitive to changes in plasma leptin levels. Therefore, using the DREADD technology in this study, we aim to understand the impact of specific neuronal modulation of CRFPVN and AgRPARC on the HPA axis activity of diet induced obese animals.