Maintenance of body temperature is achieved partly by modulating lipolysis by a network of complex regulatory mechanisms. Lipolysis is an integral part of the glycerolipid/free fatty acid (GL/FFA) cycle, which is the focus of this review, and we discuss the significance of this pathway in the regulation of many physiological processes besides thermogenesis. GL/FFA cycle is referred to as a "futile" cycle because it involves continuous formation and hydrolysis of GL with the release of heat, at the expense of ATP. However, we present evidence underscoring the "vital" cellular signaling roles of the GL/FFA cycle for many biological processes. Probably because of its importance in many cellular functions, GL/FFA cycling is under stringent control and is organized as several composite short substrate/product cycles where forward and backward reactions are catalyzed by separate enzymes. We believe that the renaissance of the GL/FFA cycle is timely, considering the emerging view that many of the neutral lipids are in fact key signaling molecules whose production is closely linked to GL/FFA cycling processes. The evidence supporting the view that alterations in GL/FFA cycling are involved in the pathogenesis of "fatal" conditions such as obesity, type 2 diabetes, and cancer is discussed. We also review the different enzymatic and transport steps that encompass the GL/FFA cycle leading to the generation of several metabolic signals possibly implicated in the regulation of biological processes ranging from energy homeostasis, insulin secretion and appetite control to aging and longevity. Finally, we present a perspective of the possible therapeutic implications of targeting this cycling.

中文翻译：

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甘油脂代谢和健康与疾病中的信号传递。

维持体温部分通过复杂调控机制网络调节脂解作用来实现。脂解是甘油脂/游离脂肪酸（GL / FFA）循环的组成部分，这是本综述的重点，我们讨论了该途径在调节生热作用之外的许多生理过程中的重要性。GL / FFA循环称为“无效”循环，因为它涉及GL的连续形成和水解以及放热，但以ATP为代价。但是，我们目前的证据强调了许多生物过程中GL / FFA循环的“重要”细胞信号传导作用。可能是由于其在许多细胞功能中的重要性，GL / FFA循环受到严格控制，并组织为多个复合短底物/产物循环，其中正向和反向反应由单独的酶催化。我们认为，鉴于许多中性脂质实际上是其产生与GL / FFA循环过程密切相关的关键信号分子的新观点，GL / FFA循环的复兴是及时的。讨论了支持以下观点的证据：GL / FFA循环的改变与肥胖，2型糖尿病和癌症等“致命”疾病的发病机制有关。我们还回顾了包括GL / FFA循环在内的不同酶促和转运步骤，这些步骤导致产生了一些代谢信号，这些信号可能与能量动态平衡等生物过程的调控有关，胰岛素的分泌和食欲可控制衰老和长寿。最后，我们提出了针对该循环可能产生的治疗意义的观点。