Biophysical and genetic cues regulating the structural remodeling of adipose tissue upon caloric excess

Abstract Obesity is an alarmingly common and serious disease. Adipose tissue stores excess calories as triacylglycerol (TAG) and cholesteryl ester in lipid droplets (LDs). How fat packing is regulated in the different adipose depots (white versus brown) and how diet composition alters this packing remain poorly understood. Using small-angle X-ray scattering, we show that LDs are liquid-crystalline, packing TAG in a disordered core with a multilamellar crystalline shell. Western diet increases the number of TAG lamellae in both the depots, while high fat diet alters only the white adipose. Consistently, collagen packs randomly in white fat, forming a permissive environment for LD expansion but is highly oriented in brown fat. During obesity, decrease in chenodeoxycholic acid (CDCA), the endogenous bile acid ligand of Farnesoid X receptor (FXR) is noted. Moreover, FXR deletion leads to enlarged adipocytes, whereas addition of CDCA promotes LD breakdown. These findings uncover that BAs, diet, and tissue niche dictate LD structural remodeling.