Research progress on mitochondria-lipid droplet coupling and its regulation of lipid metabolism and obesity

Mitochondria-lipid droplet coupling (MLC) is a key structural interface linking intracellular lipid storage with energy utilization and metabolism. The development and progression of obesity are fundamentally driven by an imbalance between energy intake and expenditure. MLC plays critical roles in regulating lipid mobilization, fatty acid oxidation, and thermogenesis in adipose tissue, although its molecular mechanisms and clinical translational value remain to be fully elucidated. The functions of MLC are context dependent and may be bidirectional: in different cell types or metabolic states, interactions mediated by specific coupling protein complexes may preferentially promote either fatty acid oxidation or lipid synthesis. Studies have shown that MLC and peridroplet mitochondria (PDM) not only participate in lipid mobilization by accelerating lipid droplet breakdown and facilitating the directed transfer of fatty acids but also serve as key nodes in maintaining non-shivering thermogenesis in adipose tissue and increasing energy expenditure. Future studies should further clarify the molecular mechanisms underlying the metabolic functional specificity of MLC mediated by different protein complexes and explore its specific roles in adipose tissue. Such efforts may provide new therapeutic strategies targeting MLC for the treatment of obesity and related metabolic disorders.