Lipid trafficking and signaling in adipocytes

Adipose tissue is a highly plastic organ that plays a central role in regulating whole body energy metabolism. The capacity for adipocytes to store chemical energy in lipid droplets (LDs) protects other organs against the toxic effects of ectopic lipid deposition. Excessive free fatty acids (FFAs) can be esterified into triacylglycerol (TAG) and accumulate within intracellular LDs, which are considered to take place in the endoplasmic reticulum (ER), where neutral lipids are synthesized and packaged in lens-like structures. Lipids in the adipocytes are important biomolecules and serve numerous vital biological functions, which can be identified and quantified by lipidomics. The effects of diet, exercise, or cold exposure on adipose tissue have shown several specific thermogenic biomarkers in lipids, such as cardiolipin and ceramide. Thus, lipids and LDs facilitate the coordination and communication between different organelles and organs, and thus, act as vital mediators of cellular metabolism. Adipocytes make up more than 90% of adipose tissue volume; however, they represent less than 50% of its cellular content. The connective tissue surrounding adipocytes contains the stromal vascular fraction (SVF) and harbors adipose progenitor cells (APCs), which are the cells that give birth to mature adipocytes, together with immune cells and vasculature, which assure overall tissue homeostasis. Using mosaic lineage labeling and single-cell sequencing, progenitor subtypes were identified to modulate adipogenic capacity through paracrine mechanisms. During the APC differentiation, over two dozen transcription factors have been shown to play important roles in adipocyte development. However, the mechanisms of each subtype and the relationships between these mechanisms and metabolic disease susceptibility are incompletely understood.