microRNAs in Action: Regulation of Feeding Behavior

Overview

Glutamate is a major neurotransmitter involved in signaling in the brain including between the paraventricular nucleus of the hypothalamus and nucleus accumbens. Caloric intake is regulated by these structures. Thus, dysregulation of this process can lead to overconsumption, causing obesity. Vesicular glutamate transporter (VGLUT) levels regulate packaging of glutamate. VGLUT transcripts are regulated by microRNAs (miRNA), which play key roles in the post -transcriptional regulation of gene expression. miRNA sponges contain numerous high-affinity binding sites for a specific miRNA to prevent it from binding to its target. In this project, we tested the hypothesis that higher levels of glutamate released by VPM4 neurons promote feeding, and that glutamate lev els were regulated by miR -1000 and miR -1008, which target VGLUT. Using the binary Gal4-UAS system to express miRNA sponges in just one pair of neurons in the Drosophila brain, the VPM4 neurons, we conducted assays with control groups and experimental groups. There was significantly less food intake in the experimental group with miR -1008 knockdown in VPM4 neurons, suggesting that glutamate functions here as an inhibitory neurotransmitter. There was no difference in food intake for flies with miR -1000 knockd own indicating specificity in miRNA function, narrowing down which miRNAs may be most effective in potential treatments. Overall, this project demonstrates miRNA-1008 regulates food intake and further experiments will demonstrate this regulation is through VGLUT and glutamate. These findings can be used to further research on effective and non - invasive treatments for human obesity. Kentucky

Competition history

• JSHS 2024 Category not listed

Resources

• National JSHS abstract book ↗

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