Fibroblast Growth Factor 13 Regulates Thermogenesis and Metabolism
Date
2019
Authors
Advisors
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Abstract
The non-secreted fibroblast growth factor (FGF) homologous factor (FHF) FGF13 is a noncanonical FGF with identified roles in neuronal development, pain sensation, and cardiac physiology, but recent reports suggest broader roles. The in vivo functions of FGF13 have not been widely studied. In this study, we have generated a global heterozygous Fgf13 knockout mouse model. In these animals, we observed hyperactivity and accompanying reduced core body temperature in mice housed at 22 °C. In mice housed at 30 °C (thermoneutrality) we observed development of a pronounced obesity. Defects in thermogenesis and metabolism were found to be due to impaired central nervous system regulation of sympathetic activation of brown fat. Neuronal and hypothalamic specific ablation of Fgf13 recapitulated weight gain at 30 °C. In global heterozygous animals, norepinephrine turnover in brown fat was reduced at both housing temperatures, while direct activation of brown fat by a β3 agonist showed an intact response. Further, we found that FGF13 is a direct regulator of NaV1.7, a hypothalamic Na+ channel associated with regulation of body weight. Our data expand the physiologic roles for FGF13, and enhance the understanding of the multifunctional FHFs.
Type
Department
Description
Provenance
Citation
Permalink
Citation
Sinden, Daniel Stephen (2019). Fibroblast Growth Factor 13 Regulates Thermogenesis and Metabolism. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/18646.
Collections
Except where otherwise noted, student scholarship that was shared on DukeSpace after 2009 is made available to the public under a Creative Commons Attribution / Non-commercial / No derivatives (CC-BY-NC-ND) license. All rights in student work shared on DukeSpace before 2009 remain with the author and/or their designee, whose permission may be required for reuse.