Diet-Induced Obesity Modulates Close-Packing of Triacylglycerols in Lipid Droplets of Adipose Tissue

Adipose-derived lipid droplets (LDs) are rich in triacylglycerol (TAGs), which regulate essential cellular processes such as energy storage. Although TAG abundance in adipocytes has been linked to metabolic disorders, including obesity and metabolic syndromes, how LDs dynamically package TAGs in response to excessive nutrients remains elusive. Here, we found that LD lipidomes display a remarkable increase in TAG acyl chain saturation under calorie-dense diets turning them conducive to close-packing. Using high-resolution X-ray diffraction, solid-state NMR, and imaging, we show that beyond size expansion, LDs from mice under varied obesogenic diets govern fat accumulation by packing TAGs in different crystalline polymorphs. Consistently, LD membrane tension and tissue elastic modulus in high-calorie-fed mice doubled compared to normal diet. Our data suggest that in addition to expanding, adipocyte LDs undergo structural remodeling in response to caloric overload, close-packing rigid and highly saturated TAGs. This work could enable the development of new therapeutics for LD-involved pathologies.