Fat cell lipolysis control

Bezaire and Langin have produced a very good review of the hormonal regulation of adipocyte lipolysis
White adipose tissue is an unlimited pool of energy. In White adipose tissue non esterified fatty acids originating from dietary intake or de novo synthesis are stored as triacylglycerides in highly-structured hydrophobic lipid droplets (LD). As a consequence of its its storage capacity and ability to hydrolyse triacylglycerides (a process termed lipolysis) White adipose tissue provides a non esterified fatty acids buffering system for other organs. Lipolysis is the breakdown of one triacylglyceride molecule to three energy-rich non esterified fatty acids and one glycerol molecule, which are released into the bloodstream and are available for uptake by other tissues. non esterified fatty acids are not only an energy source, they are also signalling molecules. An excess of non esterified fatty acids can interfere with normal metabolism, which happens in obesity and type 2 diabetes. Chronically increased non esterified fatty acids alter glucose and lipid metabolism in skeletal muscle and liver and may lead to insulin resistance
Tight regulatory control of lipolysis is provided by cateholamines and insulin. Adrenaline and the neurotransmitter noradrenaline stimulate lipolysis through the activation of β1- and β2-adrenergic receptors. Coupling of β1- and β2- adrenergic receptors to stimulatory GTP-binding protein receptors activate adenylyl cyclase, increasing cAMP production. A rise in cAMP activates protein kinase A, “which phosphorylates hormone sensitive lipase and LD-coating protein perilipin to stimulate lipolysis. Conversely, catecholarnines can inhibit lipolysis through the activation of α2-AR and their coupling to inhibitory GTP binding protein receptors. The latter inhibit adenylyl cyclase action and cAMP production. Thus, – adrenergic receptors -dependent lipolysis is dictated by the combined effects of pro-lipolytic β-adrenergic receptors and anti-lipolytic α2- adrenergic receptors. Impairment in protein kinase A-stirnulated lipolysis observed in obesity is thought to result from increased stimulation of α-2 – adrenergic receptors. Insulin also regulates lipolysis when binding to its receptor on adipocytes. Insulin binding to insulin receptor substrate 1 leads to phosphodiesterase 3B activation, which degrades cAMP, and consequently reduces PKA activation. Thus, in a postprandial state insulin not
only favours substrate uptake and storage but also minimizes triacylglyceride breakdown in adipocytes.
In human fat cells an additional signal transduction pathway, independent of catecholamines and insulin, is implicated in pro-lipolytic events. Natriuretic peptides bind type A receptors, which possess intrinsic guanylyl cyclase activity . Increases in cGMP activate Protein Kinase G, which similarly to Protein Kinase A phosphorylates hormone sensitive lipase and protein perilipin . Stimulation of lipolysis by natriuretic peptides is of similar magnitude to that of catecholarnines and is particularly pronounced during exercise.
Natriuretic peptides, catecholamines and insulin provide the main regulatory control of lipolysis in human adipocytes. Additional hormones and factors such as growth hormone, TNFa, and IL-6 also influence lipolysis by altering the signalling pathways or lipolytic machinery. There is also a wealth of anti-lipolytic systems activated by catecholamines, adenosine, PG and metabolites for which the physiological relevance is still unknown.
Bezaire and Langin 2009 Regulation of adipose tissue biology. Proceedings of the Nutrition Society vol 68 pp 350-360

Martin Eastwood
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