Effect of acute optogenetic and chronic chemogenetic activation of AT1a receptors in paraventricular nucleus neurons on energy metabolism in high-fat diet animals

• Grant number: 22/00977-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 01, 2022
• End date: May 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Débora Simões de Almeida Colombari
• Grantee: Jéssica Matheus de Sá
• Supervisor: Annette Diane de Kloet
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Florida, Gainesville (UF), United States
• Associated to the scholarship: 19/22767-8 - Mechanisms involved in the cardiovascular and hydroelectrolytic changes induced by central Angiotensin II and osmoreceptors in rats fed with a high-fat diet, BP.DR

Abstract

Obesity is defined as the excessive accumulation of fat that causes damage to the health of the individual. In recent decades, some factors have been attributed to weight gain, such as increased intake of highly energetic foods that are high in fat and an increase in physical inactivity. High-fat diet induced-obesity leads to a greater activation of the renin-angiotensin system including the RAS located in the brain and in the adipocytes leading, therefore, to the increase of angiotensin II (ANG II) peripherally and in the brain. ANG II acting on AT1 receptors in the central nervous system (CNS) is involved in the maintenance of different types of hypertensions including obesity related hypertension. Data from Dr. De Kloet's group showed that AT1a receptors (AT1aR), seem to be involved in the control of food intake. The deletion of AT1aR from the paraventricular nucleus of the hypothalamus (PVN) neurons, important area, which is very active during obesity, exacerbates diet-induced obesity, in part, by increasing food intake, but whether such activation directly influences food intake or body weight under basal or obese conditions remains to be discerned. Thus, the following project aims to verify the central circuits by way of ANG II and the AT1aR receptor act within the PVN coordinating ingestive responses during obesity. These experiments will utilize the Cre-Lox system, virally mediated gene transfer and in vivo optogenetics and chemogenetic to test the hypothesis that acute/chronic activation of AT1aR neurons in the PVN will decrease food intake and this effect will be enhanced in mice rendered obese on a high-fat diet. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

DE SA, JESSICA; ELSAAFIEN, KHALID; SCOTT, KAREN; COLOMBARI, DEBORA; KRAUSE, ERIC; DE KLOET, ANNETTE. Anatomical mapping of 'angiotensin sensitive' hypothalamic circuits: implications for the neural control of energy balance. PHYSIOLOGY, v. 38, p. 2-pg., 2023-05-01. (19/22767-8, 22/00977-3)

DE SA, JESSICA; ELSAAFIEN, KHALID; JOHNSON, DOMINIQUE; COLOMBARI, DEBORA S. A.; SCOTT, KAREN. The impact of chronic chemogenetic activation of ATlaR neurons in the PVN on energy balance and fluid intake. PHYSIOLOGY, v. 39, p. 2-pg., 2024-05-01. (22/00977-3, 19/22767-8)