Cloning of a novel lipase that is Induced by fasting and promotes lipolysis in adipocytes.

Hiroaki Okazaki, Jun-ichi Osuga, Masaki Igarashi, Makiko Tajima, Makiko Nishi, Motohiro Sekiya, Sachiko Okazaki, Naoya Yahagi, Kazuhisa Tsukamoto, Michiyo Amemiya-Kudo, Takashi Matsuzaka, Hitoshi Shimano, Nobuhiro Yamada, Junken Aoki, Hiroyuki Arai, Shun Ishibashi, Takashi Kadowaki

Adipocytes store triacylglycerol (TG) in the period of energy excess, and release free fatty acids (FFAs) through the hydrolysis of TG in the period of energy depletion, providing energy to peripheral tissue, thus regulating whole body energy balance. Despite the presumed pivotal role of TG lipase (TGL) in these metabolic processes, the molecular identity and function of TGL are not fully understood. We have previously shown that TGL(s) other than hormone-sensitive lipase (HSL), which is previously believed to be the primary TGL in adipocytes, play an important role in lipolysis in adipocytes by using HSL-deficient mice. To identify such TGL(s) in adipocytes, we have screened public database for a known lipase consensus motif, followed by screening for the enzymatic activity toward TG. We have cloned one novel lipase that is expressed in adipose tissue, liver, and intestine, and increased during the differentiation of 3T3-L1 adipocytes, and has substantial TGL activity and negligible neutral cholesterol ester hydrolase activity; all of these are known property of adipocyte TGL other than HSL. Furthermore, mRNA expression of this TGL in mouse adipose tissue is (1) induced by fasting, (2) decreased in ob/ob mice, (3) increased in streptozotocin-treated mice, suggesting a possible role of this TGL in these pathophysiological conditions. Furthermore, adenovirus-mediated overexpression of this TGL in 3T3-L1 adipocytes significantly increases lipolysis compared to control cells (P < 0.05), as assessed by the measurement of FFA and glycerol released into the media after stimulation with 10 ƒŞM of isoproterenol. In conclusion, we have identified a novel TGL that mediates lipolysis in adipocytes, and expression pattern of this TGL suggests its involvement in the pathophysiology of obesity and related disorders.