Dietary-induced obesity has become one of the major concerns in the developed world and its cost to human health is staggering. Research for over a decade has supported the idea that there is the ability of the taste system to respond to the chemosensory cures in dietary fat - consistent with their being a taste of fat. Given the role of the taste system in the hedonics of food intake, it is not a stretch to suggest the sensory cues for fat are contributing to the epidemic of obesity. Despite this important link, there is little kown about the nature of the receptors for the primary stimuli for fat chemoreception, free fatty acids, and what is known is somewhat controversial. To fill this critical void in our understanding about fatty acid signaling in the taste system, we propose to characterize previously identified receptors for all the major classes of fatty acid to provide a picture about the specificity of fat signaling in the taste system and correlate this receptor cell activity with behavior in mouse models. Specifically, we will test the general hypothesis that mammalian gustatory cells respond to fatty acids representing all the major classes of fatty acids through specific dedicated G protein-coupled receptors. The following specific aims will be examined in a multidisciplinary fashion:
SPECIFIC AIM 1. Identification of the cognate receptors for polyunsaturated fatty acids.
SPECIFIC AIM 2. The role of GPR84 in the transduction of medium chain fatty acids.
SPECIFIC AIM 3. The effectiveness of short chain fatty acids as gustatory stimuli. Completion of these three aims will profoundly enhance our understanding of the ability of the gustatory system to respond to the chemical cues contained in dietary fat and provide evidence as to the role of putative fatty acid receptors identified in the taste system in this process.
This project focuses on the gustatory receptor for the various classes of fatty acids. It will attempt for the first time to provide insight as the specificity of gustatory receptor cells to the various classes of fatty acids and the correlation of this activity with gustatory behavior in mouse models. Given that the epidemic of obesity is tied, at least in part, to overconsumption of high fat diets, understanding the mechanisms the body uses to recognize and respond to dietary fat and how these chemosensory pathways contribute to the control of food (i.e. fat) intake is critical. The outcomes of these experiments will identify the at stimuli and their cognate receptors that may allow the design of rationale, empirically-based substitutes to mimic the oral exposure to fat and in that way help control fat-induced dietary obesity.