Improving obesity research: Unveiling metabolic pathways through a 3D In vitro model of adipocytes using 3T3-L1 cells

• Published in: PloS one Vol. 19; no. 5; p. e0303612
• Main Authors: Avelino, Thayna Mendonca, Provencio, Marta García-Arévalo, Peroni, Luis Antonio, Domingues, Romênia Ramos, Torres, Felipe Rafael, de Oliveira, Paulo Sergio Lopes, Leme, Adriana Franco Paes, Figueira, Ana Carolina Migliorini
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31-05-2024; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipose tissue; Animal models; Animals; Body fat; Cell culture; Cell Differentiation; Energy storage; Ethylenediaminetetraacetic acid; Global health; Health aspects; Innovations; Insulin resistance; Metabolic disorders; Metabolic Networks and Pathways; Metabolic pathways; Metabolic syndrome; Mice; Mice, Inbred C57BL; Obesity; Obesity - metabolism; Physiological aspects; Proteomics; Proteomics - methods; Public health; Spheroids; Spheroids, Cellular - metabolism; Therapeutic applications; Three dimensional models; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Type 2 diabetes; World health; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0303612

Obesity, a burgeoning global health crisis, has tripled in prevalence over the past 45 years, necessitating innovative research methodologies. Adipocytes, which are responsible for energy storage, play a central role in obesity. However, most studies in this field rely on animal models or adipocyte monolayer cell cultures, which are limited in their ability to fully mimic the complex physiology of a living organism, or pose challenges in terms of cost, time consumption, and ethical considerations. These limitations prompt a shift towards alternative methodologies. In response, here we show a 3D in vitro model utilizing the 3T3-L1 cell line, aimed at faithfully replicating the metabolic intricacies of adipocytes in vivo. Using a workable cell line (3T3-L1), we produced adipocyte spheroids and differentiated them in presence and absence of TNF-α. Through a meticulous proteomic analysis, we compared the molecular profile of our adipose spheroids with that of adipose tissue from lean and obese C57BL/6J mice. This comparison demonstrated the model's efficacy in studying metabolic conditions, with TNF-α treated spheroids displaying a notable resemblance to obese white adipose tissue. Our findings underscore the model's simplicity, reproducibility, and cost-effectiveness, positioning it as a robust tool for authentically mimicking in vitro metabolic features of real adipose tissue. Notably, our model encapsulates key aspects of obesity, including insulin resistance and an obesity profile. This innovative approach has the potential to significantly impact the discovery of novel therapeutic interventions for metabolic syndrome and obesity. By providing a nuanced understanding of metabolic conditions, our 3D model stands as a transformative contribution to in vitro research, offering a pathway for the development of small molecules and biologics targeting these pervasive health issues in humans.