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Dynamic Proteomics of Human Adipogenesis

Explore the world of energy storage in living organisms, where ongoing research is uncovering the complexities of adipocyte differentiation and lipid metabolism. Scientists are using proteomic analyses and machine learning techniques to gain insights into the key proteome dynamics, metabolic pathways, and protein functions involved in adipogenesis. Witness the remodeling of cellular processes and discover the spatial organization of adipocytes and the secrets of organelle remodeling during fat storage. We present the results of a new study - embark on a quest to better understand adipocyte biology and its impact on obesity-related metabolic disorders.

Exploring the Capacity of Living Organisms to Store Energy: The Significance of Adipocyte Differentiation and Lipid Metabolism

The ability of living organisms to store energy in the form of fat, particularly in lipid droplets (LDs), plays a crucial role in metabolic health. Adipose tissue, specifically white adipose tissue (WAT), serves as the primary site for fat storage in the human body. Understanding the process of adipocyte differentiation, lipid storage, and mobilization is essential for studying metabolic disorders related to obesity. While transcriptomics has provided valuable insights into adipogenesis, proteomic analysis remains crucial to capture the dynamic changes and subcellular organization during this process. This study aims to fill the gap in our understanding by generating a spatiotemporal proteomic map of human adipocytes and unraveling the core proteome dynamics, metabolic pathways, and specific protein functions involved in adipogenesis.

Comprehensive Analysis of Protein Expression and Localization during Adipogenesis

Our systematic approach gives insights into cellular remodeling and the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and highlights the coordinated regulation of protein localization and abundance during adipogenesis.
Felix Klingelhuber, Scott Frendo-Cumbo, Omar Hmeadi, Austin James Taylor, Pamela Kakimoto, Sara Ribicic, Morgan Couchet, Martin Wabitsch, Timo Dirk Mueller, Mikael Ryden, Niklas Mejhert, Natalie Krahmer. doi: https://doi.org/10.1101/2023.07.01.547321

The study employed quantitative proteomic analysis and machine learning-based approaches to investigate temporal changes in protein expression and localization during adipocyte differentiation. Key findings include:

  1. Temporally resolved core proteome: Through proteomics analysis at multiple time points during adipogenesis, the researchers identified 3,934 proteins significantly regulated during the process. Principal component analysis revealed universal proteomic features, indicating conserved temporal trajectories across different adipocyte models.

  2. Hierarchical clustering analysis: Distinct clusters representing early, intermediate, and late responses during adipogenesis were identified. This comprehensive remodeling of cellular processes during adipogenesis demonstrated specific functional pathway regulation over time.

  3. Spatial map of adipogenesis: Protein correlation profiling enabled the generation of cellular maps, assigning proteins to specific organelle clusters in both mature adipocytes and pre-adipocytes. The researchers confidently assigned proteins to specific organelle distributions, providing insights into the spatial organization of adipocytes.

  4. Protein localization changes: Integration of spatial proteomics data with the time-resolved core proteome data unveiled organelle remodeling during adipogenesis. This included an increase in mitochondrial, endoplasmic reticulum, endosomal, and LD proteins, while the proportion of cytosolic, nuclear, and ribosomal proteins decreased.

  5. Identification of C19orf12: By integrating the LD-specific proteome with the core proteome data, the study discovered C19orf12 as a highly conserved LD protein upregulated during adipogenesis. C19orf12 was found to be involved in lipid droplet metabolism, and its expression in WAT showed an inverse correlation with obesity-related clinical parameters.

Unveiling Cellular Remodeling and Metabolic Changes in Adipogenesis

The study provides a comprehensive understanding of the proteomic changes and organelle reorganization during human adipogenesis. The findings shed light on the core proteome dynamics, metabolic pathways, and the role of specific proteins in adipocyte lipid storage and metabolism. Moreover, the identification of C19orf12 as an LD protein with implications for obesity-related metabolic disorders highlights the clinical relevance of the study.

Advancing Our Understanding of Adipocyte Biology through Proteomic Analysis

This research expands our knowledge of the dynamic proteomics underlying human adipogenesis. The study's comprehensive cellular map offers valuable insights into protein expression, metabolic pathways, and organelle composition during adipogenesis. These findings enhance our understanding of adipocyte biology and contribute to the study of lipid metabolism and metabolic disorders associated with obesity.