Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

    1. Sten Lund2
    1. 1The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, Denmark
      2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, Denmark
      3Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark
    1. Correspondence should be addressed to T S Nielsen; Email: thomas.nielsen{at}sund.ku.dk


    Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein–protein interactions, and protein stability/degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.

    • Revision received 14 February 2014
    • Accepted 25 February 2014
    • Made available online as an Accepted Preprint 27 February 2014
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