Ubiquitin-like modifications in adipose tissue development and obesity: New insights

Obesity involves abnormal adipose tissue remodeling, including increased fat cell number (hyperplasia) and size (hypertrophy), along with dysregulated adipogenesis, function, and turnover of white, beige, and brown fat cells. These changes cause chronic inflammation and insulin resistance, leading to metabolic diseases. Post-translational modifications (PTMs), especially ubiquitin and ubiquitin-like modifications (UBLs), regulate adipose development by attaching to proteins, affecting their activity, stability, and localization through a cascade involving E1, E2, and E3 enzymes. Although UBL modifications in adipose biology are gaining attention, their roles are only beginning to be understood. This review covers core UBLs like SUMO, NEDD8, ISG15, UFM1, ATG8/ATG12, and FAT10, and their influence on fat cell development, differentiation, function, and adipose remodeling, relevant to obesity prevention and therapy. It also discusses challenges in research and advocates the use of advanced proteomic techniques to identify adipose-specific UBL targets.