Role of hypothalamic AgRP/NPY neurons in the Hypothalamus-Pituitary-Thyroid axis control in fed and fasted mice

• Grant number: 14/20704-5
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): January 01, 2015
• Effective date (End): December 31, 2015
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Rodrigo César Rorato
• Supervisor abroad: Anthony Neil Hollenberg
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Local de pesquisa : Harvard University, Boston, United States
• Associated to the scholarship: 12/18179-4 - Investigation of saturated fat acid and high-fat diet exposure on CB2 receptor signaling in microglial cells, BP.PD

Abstract

According to the World Health Organization the obesity become a global epidemic and the number of obese individuals continues to grow. Therefore understanding the complex neurocircuitry regulating food intake and energy expenditure becomes more pivotal to determining effective treatments and therapies against obesity. The hypothalamic-pituitary-thyroid (HPT) axis, composed by thyrotropin-releasing hormone (TRH) produced in the paraventricular nucleus (PVH), which modulates the thyroid-stimulating hormone (TSH) production in the pituitary which in turn regulates the thyroid hormone (TH) circulating levels, is a key component in the regulation of basal metabolism, energetic expenditure and body temperature. It is known that nutritional stress such as long-term caloric restriction modulates HPT axis leading to a decrease in TH levels, which are secondary to a fall in leptin levels. In a recent study, using mice with selective deletion of NPY and melanocortin 4 receptor (MC4R) expression, Dr Hollenberg's group has demonstrated that fasting-induced suppression of thyroid hormone levels is controlled by both NPY and the MC4R, controlling both central suppression through the HPT axis and peripheral thyroid hormone metabolism via the liver. The hypothalamic arcuate nucleus (ARC) contains neurons expressing both NPY/Agouti-related protein [AgRP; MC4R antagonist] and proopionmelanocortin (POMC), the precursor of the alpha-melanocyte stimulating hormone [±MSH; a MC4R agonist]. In the present study we intend to investigate whether the AgRP/NPY neurons in the arcuate nucleus are the subset of neuron required for the fasting-induced suppression of the HPT axis. (AU)