Publication Date

2017

Document Type

Thesis

Committee Members

Eric Bennett (Other), Robert Fyffe (Other), David Ladle (Committee Member), Mark Rich (Committee Member), Christopher Wyatt (Advisor)

Degree Name

Master of Science (MS)

Abstract

The carotid bodies (CB), the primary peripheral chemoreceptors, respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin caused perturbations of intracellular calcium and membrane ion movement in isolated CB Type I cells (Pye et al, 2015) and augmented the response of the intact CB to hypoxia (Pye et al, 2016). This study's aim was to examine, in-vivo, if elevated leptin modulated CB function and breathing. Rats were fed high-fat chow or control chow for 16-weeks. High-fat fed (HFF) animals gained significantly more weight compared to control fed (CF) animals (n=18; p<.001; 512.56 g +/- 14.70 g vs. 444.11 g +/- 7.09 g). HFF animals also had significantly higher serum leptin levels compared to CF (n=18; p<.0001; 3.05 ng/mL +/- 0.24 ng/mL vs. 1.29 ng/mL +/- 0.12 ng/mL). Whole-body plethysmography was used to test the acute hypoxic ventilatory response (HVR) in unrestrained, conscious animals. HFF animals had an attenuated 2nd-phase of the HVR when compared to CF (n=18; p<.05; 710.1 +/- 41.9 mL kg-1 min-1 vs. 855.4 +/- 44.05 mL kg-1 min-1). CB Type I cells were isolated and intracellular calcium measured; no significant differences in the cellular hypoxic responses between groups were observed. These data show differences in the 2nd-phase of the HVR caused by high fat feeding are unlikely to be caused by an action of leptin on the Type I cells. However the possibility remains that leptin may have in-vivo postsynaptic effects on the carotid sinus nerve; this remains to be investigated.

Page Count

100

Department or Program

Department of Neuroscience, Cell Biology, and Physiology

Year Degree Awarded

2017

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