Beyond the Gut
Description
GLP-1 receptor agonists have revolutionized the treatment of diabetes and obesity by regulating blood sugar and promoting weight loss. This 3D design explores the journey of the GLP-1 receptor agonist semaglutide beyond the gut, showcasing how this molecule endures over time and reaches key regions of the brain that influence addiction-related behaviors. By highlighting semaglutide's broader pathways, the piece focusses on the therapeutic potential of GLP-1 in behavioral health.
Year
2024
Project type
3D Design
Primary Audience
Educated Lay Audience
Client
Derek Ng
Medium
Web Editorial
Tools
Maya, Zbrush, Illustrator, Procreate, Photoshop, Protein Imager, UCSF Chimera, VMD
Preproduction
To prepare for the initial piece, extensive research was conducted on the structure of semaglutide and the modifications that extend its half-life. This included investigating the factors contributing to its prolonged duration of action, its impacts, and the areas of the brain semaglutide ultimately influences. The focus was to craft a cohesive narrative.
This narrative was then translated into an initial sketch derived from PDB files obtained during research. The molecular shapes were simplified and incorporated into a quick layout sketch, aiming to create a dynamic and engaging storyline.
Sketches were then further refined and a general color palette was chosen.
Production
A comprehensive sketch was developed from the initial layout sketch, where the placement of text and molecular structures was finalized, and the storyline fully established. An asset list was created to organize the elements derived from data. The molecular assets were cleaned and prepared using Chimera, polished and exported through VMD, and then imported into Maya. Additional models were sculpted in ZBrush and integrated into Maya, where materials were adjusted and applied to each model before being exported individually to preserve composition and focal length. The final scene was composited in Photoshop, and details were added in Procreate. Vector illustrations were completed in Illustrator and imported into the final piece.
References:
Aertgeerts, K., Ye, S., Tennant, M. G., Kraus, M. L., Rogers, J., Sang, B. C., Skene, R. J., Webb, D. R., & Prasad, G. S. (2004). Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation. Protein Science, 13(2), 412-421. https://doi.org/10.1110/ps.03460604; Lee, S., & Lee, D. Y. (2017). Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. Annals of Pediatric Endocrinology & Metabolism, 22(1), 15-26. https://doi.org/10.6065/apem.2017.22.1.15; Dailey, M. J., & Moran, T. H. (2013). Glucagon-like peptide 1 and appetite. Trends in Endocrinology & Metabolism, 24(2), 85-91. https://doi.org/10.1016/j.tem.2012.11.008; Dong, M., Wen, S., & Zhou, L. (2022). The relationship between the blood-brain barrier and the central effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 15, 2583-2597. https://doi.org/10.2147/DMSO.S375559; Nilvebrant, J., & Hober, S. (2013). The albumin-binding domain as a scaffold for protein engineering. Computational and Structural Biotechnology Journal, 6, e201303009. https://doi.org/10.5936/csbj.201303009; Lear, S., Amso, Z., & Shen, W. (2019). Engineering PEG-fatty acid stapled, long-acting peptide agonists for G protein-coupled receptors. Methods in Enzymology, 622, 183-200. https://doi.org/10.1016/bs.mie.2019.02.008; Eren-Yazicioglu, C. Y., Yigit, A., Dogruoz, R. E., & Yapici-Eser, H. (2021). Can GLP-1 be a target for reward system related disorders? A qualitative synthesis and systematic review analysis of studies on palatable food, drugs of abuse, and alcohol. Frontiers in Behavioral Neuroscience, 14, 614884. https://doi.org/10.3389/fnbeh.2020.614884; Richards, J. R., Dorand, M. F., Royal, K., Mnajjed, L., Paszkowiak, M., & Simmons, W. K. (2023). Significant decrease in alcohol use disorder symptoms secondary to semaglutide therapy for weight loss: A case series. The Journal of Clinical Psychiatry, 85(1), 23m15068. https://doi.org/10.4088/JCP.23m15068; Chuong, V., Farokhnia, M., Khom, S., Pince, C. L., Elvig, S., Vlkolinský, R., Marchette, R., Koob, G. F., Roberto, M., Vendruscolo, L. F., & Leggio, L. (2023). The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight, 8(12). https://doi.org/10.1172/jci.insight.170671; Adinoff, B. (2004). Neurobiologic processes in drug reward and addiction. Harvard Review of Psychiatry, 12(6), 305-320. https://doi.org/10.1080/10673220490910844;