Abstract

This study presents a comprehensive transcriptomic and proteomic atlas focused on cynomolgus monkey models of obesity and type 2 diabetes (T2D). The aim was to elucidate the molecular signatures associated with these metabolic conditions in a non-human primate species, providing insights into the pathophysiological mechanisms and potential therapeutic targets relevant to human disease. Cynomolgus monkeys with diet-induced obesity and T2D were compared to lean counterparts through high-throughput RNA sequencing (RNA-Seq) and mass spectrometry-based proteomics. The analysis revealed distinct gene expression and protein abundance patterns associated with obesity and T2D in multiple tissues, including adipose tissue, liver, and skeletal muscle. Key findings include the dysregulation of pathways related to insulin signaling, lipid metabolism, and inflammation. The identification of specific genes and proteins associated with adiposity and glucose homeostasis provides a valuable resource for understanding the molecular underpinnings of obesity-related T2D in primates.

Moreover, this atlas facilitates cross-species comparisons, highlighting conserved molecular signatures between cynomolgus monkeys and humans with obesity and T2D. The integration of transcriptomic and proteomic data enhances our understanding of the complex interplay between genetic, transcriptional, and post-translational factors in the context of metabolic disorders. The presented transcriptomic and proteomic atlas serves as a foundational resource for future studies aiming to unravel the intricate molecular mechanisms contributing to obesity and T2D. The identified molecular signatures may inform the development of targeted interventions and therapeutic strategies for these prevalent metabolic conditions in both non-human primates and humans.