The objective of this proposal is to gain insight into the central mechanisms underlying the regulation of sympathetic control of brown adipose tissue (BAT). Sympathetic outflow to BAT plays a critical role in thermoregulation and contributes significantly to the regulation of energy expenditure. Impairments or alterations in the regulation of sympathetic output to BAT are associated with potentially life threatening pathological conditions and disease states such as hyperthermia and obesity.
The specific aims of this proposal are to determine the specific central nervous system pathways involved in the regulation of sympathetic outflow to BAT during the febrile response. Inhibition of areas implicated in the regulation of sympathetic outflow to BAT will be performed during experimentally induced fever in order to assess their involvement in the febrile response. In addition, the activity of single neurons within areas found to be necessary for the febrile response will be recorded during various physiological and pharmacological manipulations in order to gain a greater understanding of the circuits involved in febrile thermogenesis. Insights gained from these experiments may eventually lead to novel approaches for treating the pathological conditions resulting from disregulation of BAT.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK065401-02
Application #
6883969
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2004-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Morrison, Shaun F; Madden, Christopher J; Tupone, Domenico (2012) Central control of brown adipose tissue thermogenesis. Front Endocrinol (Lausanne) 3:
Madden, Christopher J; Morrison, Shaun F (2010) Endogenous activation of spinal 5-hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 298:R776-83
Madden, C J; Morrison, S F (2009) Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 296:R831-43
Madden, C J; Morrison, S F (2008) Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord. Neuropharmacology 54:487-96
Morrison, Shaun F; Nakamura, Kazuhiro; Madden, Christopher J (2008) Central control of thermogenesis in mammals. Exp Physiol 93:773-97
Adams, Julye M; Madden, Christopher J; Sved, Alan F et al. (2007) Increased dietary salt enhances sympathoexcitatory and sympathoinhibitory responses from the rostral ventrolateral medulla. Hypertension 50:354-9
Madden, Christopher J; Morrison, Shaun F (2006) Serotonin potentiates sympathetic responses evoked by spinal NMDA. J Physiol 577:525-37
Madden, C J; Morrison, S F (2005) Hypoxic activation of arterial chemoreceptors inhibits sympathetic outflow to brown adipose tissue in rats. J Physiol 566:559-73