Hormonal Regulation of Lipolysis in Adipose Tissue

Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the hydrolytic action of lipases, with the release of fatty acids (FA) that are used by other tissues during times of energy deprivation. Unlike synthesis of TAG, which occurs not only in adipose tissue but also in other tissues such as liver for VLDL formation, hydrolysis of TAG, lipolysis, predominantly occurs in adipose tissue. Until recently, hormone sensitive lipase (HSL) was considered to be the key rate-limiting enzyme responsible for regulating TAG mobilization. However, recent studies on HSL-null mice have challenged such a concept. A novel lipase named desnutrin/ATGL has been recently discovered to play a key role in lipolysis in adipocytes. Lipolysis is under tight hormonal regulation. Although opposing regulation of lipolysis in adipose tissue by insulin and catecholamines is well understood, autocrine/paracrine factors may also participate in its regulation. Intricate cooperation of these endocrine and autocrine/paracrine factors leads to a fine regulation of lipolysis in adipocytes, needed for energy homeostasis. In this review, we summarize and discuss the recent progress made in the regulation of adipocyte lipolysis. 3 Adipocytes play a critical role in energy homeostasis by hydrolysis (lipolysis) of their triacylglycerol (TAG) reserves to provide fatty acids (FA) that are important oxidative fuels for other tissues during times of energy deprivation such as fasting and exercise. A dysregulation of lipolysis may lead to metabolic abnormalities. Reduced lipolytic activity may contribute to accumulation of TAG in adipose tissue and thus obesity. On the other hand, excessive lipolysis may contribute to lipodystrophy syndromes, which are characterized by a significant loss or redistribution of TAG in adipose tissue depots, which may lead to higher circulating FA and ectopic storage of TAG. These abnormalities are associated with the development of insulin resistance. Thus, fine regulation of lipolysis is crucial for maintenance of body energy homeostasis as well as for the prevention of metabolic diseases. During the lipolytic process, one molecule of glycerol and three molecules of FA are produced by the hydrolysis of one molecule of TAG. FA are released into the circulation to be taken up by other tissues. FA can also be oxidized or used for reesterification in adipocytes to produce TAG. Lipolysis is under tight regulation by hormones, catecholamines and insulin, of which secretion is under nutritional regulation. For many years, hormone sensitive lipase (HSL) has been considered to be the regulatory enzyme, hydrolyzing FA from sn-1 …