Date of Award:
Doctor of Philosophy (PhD)
Timothy A. Gilbertson
Given the dramatic rise in obesity and the diseases linked with it, it is becoming increasingly important to understand the mechanisms that underlie the body's ability to recognize fat. The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that relays the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to activate trigeminal ganglionic neurons has remained unexplored. In general, my research has provided the first evidence of fatty acids activating the somatosensory system by increasing the intracellular calcium concentration and generating receptor potentials. Other experiments were focused on identifying fatty acids-responsive pathways in acute isolated trigeminal neurons involved with fat somatosensory perception. My results revealed that fatty acids-activated pathways involved the release of intracellular calcium stores in subpopulations of trigeminal neurons. By using pseudorabies virus as a "live-cell" tracer, a subpopulation of lingual-innervated trigeminal neurons was labeled. Quantitative real-time polymerase chain reaction on individual neurons showed several transient receptor potential channel markers were expressed in these labeled neurons, which indicated the identification of lingual-innervated neurons was successful. This technique helped resolve the problem of trigeminal neurons being a mixed population of cells, and confirmed the role of the release of intracellular calcium stores in fatty acid-activated pathways. Using patch clamp recording, I discovered that the linoleic acid activated signaling pathway involved the activation of G protein and phospholipase C. I further began to characterize the downstream conductance that is activated by linoleic acid in rat trigeminal neurons. Using perforated patch clamp recording, I have recorded linoleic acid-induced currents that exhibited many of the properties of transient receptor potential-like channels, suggesting that this "cellular sensor" is probably playing an important role in the somatosensory perception of fat. Taken together, this dissertation research has revealed the ability of fatty acids to act as effective tactile stimuli and identified several elements of the fatty acids-activated signaling pathway involved in the somatosensory perception of fat.
Yu, Tian, "Targeting Fatty Acid-Activated Pathways in the Somatosensory System" (2010). All Graduate Theses and Dissertations. Paper 687.
Copyright for this work is retained by the student.