Metabolic phenotyping of mice devoid of neuropeptide Y (NPY) specifically in sympathetic neurons

Abstract

The brain, particularly the hypothalamus, integrates central and peripheral signals to control several autonomic functions, including the body's energy balance. This regulation occurs in a synchronized way and depends on neural connections, particularly of sympathetic efferents that regulate the functions of the pancreas, liver, adipose tissue, and other organs and tissues that participate in the control of the organism's global metabolism. Recent unpublished studies revealed that a subpopulation of autonomic neurons that express neuropeptide Y (NPY) innervates brown adipose tissue, thus having a relevant role in the regulation of thermogenesis. However, little is known about the role played by these autonomic fibers in the regulation of the organism's general metabolism. To explore such mechanisms, the laboratory of professor Ana Domingos, University of Oxford in the United Kingdom, developed a transgenic mouse that does not express NPY specifically in sympathetic neurons, through the deletion of NPY in neurons that express tyrosine hydroxylase (Thcre/ Npyflox). In this project, developed in partnership with the laboratory of professor Ana Domingos, we will perform the metabolic phenotyping of these mice. To this end, female and male Thcre/Npyflox mice and their C57/BL6 controls will be randomly divided into two groups, fed for 4 weeks on conventional chow or a high-fat diet containing 36% of its caloric value in the form of predominantly saturated fat. Throughout the experimental period, food intake, body mass, blood pressure, body temperature, interscapular temperature and blood glucose will be determined. At the end of the experimental period, glucose tolerance, insulin tolerance, body composition, O2 consumption, CO2 production, energy efficiency and spontaneous movement will be evaluated. Serum leptin, adiponectin, insulin, corticosterone, T4, TSH, TNF-a, IL-1b, IL-6 and IL-10 will also be measured. In white and brown adipose tissue fragments, transcripts of Ucp1, Pgc1-±, Adrb3 and Th will be determined. Finally, the histological characteristics of brown adipose tissue, liver and pancreatic islets will be analyzed. This study will contribute to advance the understanding of the role of autonomic fibers that express NPY in the global metabolic regulation. (AU)