The regulation of lipolysis in adipocytes is a complex process that is tightly controlled by hormonal and biochemical signals. Lipolysis, the hydrolysis of triacylglycerol (TAG) stores in white adipose tissue (WAT), releases glycerol and non-esterified fatty acids (FFAs) for energy use by other organs. This process is crucial for maintaining energy homeostasis and is influenced by nutritional status and nutrient intake. Key mediators of lipolysis include hormone-sensitive lipase (HSL), desnutrin/ATGL, and perilipins. HSL, a well-known lipase, is essential for DAG and TAG hydrolysis, but recent studies have identified other novel adipocyte lipases, such as desnutrin/ATGL, which play significant roles in TAG hydrolysis. Desnutrin/ATGL is regulated by fasting and is involved in mobilizing TAG stores during energy demand. Perilipins, particularly perilipin A and B, are critical in modulating basal and stimulated lipolysis by controlling access to TAG substrates and facilitating the translocation of HSL to the lipid droplet. Other proteins, such as adipose fatty acid-binding protein (aFABP), caveolin-1, and CGI-58, also contribute to lipolysis regulation. Nutritional regulation of lipolysis occurs through acute responses during fasting and refeeding, with catecholamines and glucagon stimulating lipolysis, while insulin inhibits it. Obesity is associated with increased basal lipolysis and impaired catecholamine-stimulated lipolysis, possibly due to altered insulin signaling and increased TNFα production. Dietary components like calcium, caffeine, and ethanol can also influence lipolysis. Future research will focus on understanding the roles of specific lipases and the energy sensor AMPK in mediating lipolysis.The regulation of lipolysis in adipocytes is a complex process that is tightly controlled by hormonal and biochemical signals. Lipolysis, the hydrolysis of triacylglycerol (TAG) stores in white adipose tissue (WAT), releases glycerol and non-esterified fatty acids (FFAs) for energy use by other organs. This process is crucial for maintaining energy homeostasis and is influenced by nutritional status and nutrient intake. Key mediators of lipolysis include hormone-sensitive lipase (HSL), desnutrin/ATGL, and perilipins. HSL, a well-known lipase, is essential for DAG and TAG hydrolysis, but recent studies have identified other novel adipocyte lipases, such as desnutrin/ATGL, which play significant roles in TAG hydrolysis. Desnutrin/ATGL is regulated by fasting and is involved in mobilizing TAG stores during energy demand. Perilipins, particularly perilipin A and B, are critical in modulating basal and stimulated lipolysis by controlling access to TAG substrates and facilitating the translocation of HSL to the lipid droplet. Other proteins, such as adipose fatty acid-binding protein (aFABP), caveolin-1, and CGI-58, also contribute to lipolysis regulation. Nutritional regulation of lipolysis occurs through acute responses during fasting and refeeding, with catecholamines and glucagon stimulating lipolysis, while insulin inhibits it. Obesity is associated with increased basal lipolysis and impaired catecholamine-stimulated lipolysis, possibly due to altered insulin signaling and increased TNFα production. Dietary components like calcium, caffeine, and ethanol can also influence lipolysis. Future research will focus on understanding the roles of specific lipases and the energy sensor AMPK in mediating lipolysis.