Reprogramming in delipidated adipocytes: metabolism, regulation and progress

Through specific induction protocols in vitro or under physiological or pathological conditions in vivo, mature adipocytes can be converted into mesenchymal stem cells, challenging our traditional understanding of mature adipocyte identity and cell fate determination. Given that dedifferentiated adipocytes are a rich source of stem cells in the human body, they hold great potential for applications in regenerative medicine. This review discusses the process of lipid droplet depletion and the stage-specific metabolic remodeling of intracellular substances-including triglycerides and free fatty acids, energy-related metabolites (ATP, NAD⁺/NADH, acetyl-CoA), as well as the alterations in key proteins, organelle remodeling, and epigenetic modifications. These insights provide a deeper understanding of adipocyte identity and the molecular mechanisms underlying the transition between different adipocyte differentiation stages. The review also highlights advanced techniques in the field, including adipocyte lineage-tracing models and single-cell RNA sequencing, enhancing the accuracy and precision of research while enabling the capture of dynamic changes within cells. These advancements offer a more comprehensive approach to studying dedifferentiated adipocytes.