Biophysical and Genetic Cues Regulating the Structural Remodeling of Adipose Tissue Upon Caloric Excess

Obesity is an alarmingly common and serious disease. Adipose tissue stores excess calories as triacylglycerol (TAG) and cholesterol ester in lipid droplets (LDs) and mobilizes them as needed. How adipose tissue regulates fat packing in the different depots—white versus brown—during obesity remains poorly understood. We show that adipose LDs are liquid-crystalline, packing TAG in a disordered core and a multilamellar crystalline shell. During obesity, the number of TAG lamellae increases in a manner that is adipose depot-specific. Additionally, collagen packs randomly in white fat forming a permissive environment for LD expansion, but is highly-oriented in brown fat. Finally, during obesity, there is reduced levels of chenodeoxycholic acid (CDCA), a bile-acid (BA). Loss of the BA receptor, Farnesoid X receptor (FXR) leads to enlarged adipocytes. In fact, CDCA, a major ligand of FXR, promotes LD breakdown. These findings implicate that BA profiles, diet, and tissue niche dictate LD remodeling.