Journal
NUTRITION RESEARCH REVIEWS
Volume 27, Issue 1, Pages 63-93Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S095442241400002X
Keywords
Catecholamines; Insulin; Hormone-sensitive lipase; Adipocyte TAG lipase; Perilipin; Adipokines; Lipid mobilisation
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Funding
- Spanish Instituto de Salud Carlos III
- Fondo de Investigacion Sanitaria - FEDER from the Ministerio de Economia y Competitividad [CIBERobn CB06/03/1014, FIS PI10/01677, PI12/00515]
- Plan de Investigacion de la Universidad de Navarra [PIUNA 2011-13]
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In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms.
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