Neurobiology of chemosensation, reward and eating behaviors; molecular and neuronal mechanisms along the gut-brain-axis in animal models

National Institute On Alcohol Abuse And Alcoholism

Investigators

Linked publications, trials & patents

Abstract

We are studying sensory science and metabolism in animal models of obesity and metabolic dysfunction. Metabolic Dysfunction and Sensory Science: The rise in obesity is associated with an increased availability of highly palatable and energy-dense foods rich in fat and sugar. The pleasure-driven value of energy-dense foods promotes their preferential consumption, which can lead to increased caloric intake and obesity. Taste, olfaction, and other chemosensory systems contribute to hedonic processing and eating behavior. Thus, there is growing interest in the role of taste in obesity, including studying the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions. Pre-clinical studies are necessary to test potential mechanisms underlying chemosensation that we cannot test in clinical populations. The ongoing project will allow us to understand chemosensory changes associated with diet and how sensory cues reshape brain reward circuitry. To this end, we are investigating the impact of diet and obesity on neuronal dynamics in mouse brain regions involved in chemosensation and reward (i.e., olfactory bulb, olfactory cortex, and insular cortex). Specifically, we will examine the effect of diet on behavior (e.g., taste preference and smell detection/discrimination), neuronal dynamics (e.g., neuronal activation, neuronal circuitry, and neuronal phenotype), and transcriptome and protein levels. To achieve this goal, we have been developing protocols that utilize techniques including optogenetics, electrophysiology, and transcriptomic studies. Collaborations continue with intramural and extramural collaborators. Drs. Claudia Colina-Prisco led this project in the past, and Marcel Vega is leading the ongoing subproject. Sensory System Disturbances: Opioid use disorders, including misuse of prescription pain relievers, are a national crisis with devastating consequences, including a rapidly escalating number of opioid overdose-related deaths. The physiological mechanisms underlying pain, addiction, and their intersection are not fully understood. This research aims to study genomic changes across multiple phenotypes of pain, opioid use, and opioid use disorder. The goal is to improve understanding of the relationship between disturbances in sensory systems and disease. This includes substance use disorder-induced differences in thresholds and responses to taste, olfaction, and changes in pain perception. Projects have started, and preliminary findings have been obtained. We recently published a paper in the International Journal of Molecular Sciences titled "Diet-induced obesity induces transcriptomic changes in neuroimmunometabolic-related genes in the striatum and olfactory bulb." The incidence of obesity has markedly increased globally over the last several decades, which is believed to be associated with an easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in understanding the genetic changes in the brain associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions of the brain associated with olfaction and hedonic food-seeking, respectively, in high-fat diet (HFD)-fed obese mice. To isolate the dietary effects of obesity, we also examined transcriptomic changes in standard chow- and limited HFD-fed groups, with the latter being pair-fed with an HFD isocaloric to the consumption of the normal chow-fed mice. Using RNA sequencing, we identified 274 differentially expressed genes (DEGs) in the striatum and 11 in the olfactory bulb of ad libitum HFD-fed mice compared to the chow-fed group and thirty-eight DEGs in the striatum between the ad libitum HFD- and limited-HFD-fed groups. The DEGs in both tissues were associated with inflammation and immune-related pathways, including oxidative stress and immune function, as well as mitochondrial dysfunction and reward pathways in the striatum. These results shed light on potential obesity-associated genes in these brain regions.