Abstract
Lipolysis is the pathway by which adipocyte triglycerides are hydrolyzed and mobilized as free fatty acids, during periods when energy expenditure exceeds caloric intake. Hormone-sensitive lipase is the major enzyme involved in regulation of lipolysis. Numerous hormones acutely regulate lipolysis, but the most physiologically important are insulin (inhibitory) and catecholamines (stimulatory). Hormone-sensitive lipase is activated by phosphorylation in response to stimulatory hormones through a cAMP mediated cascade. Conversely, insulin and other hormones that inhibit lipolysis decrease phosphorylation of hormone-sensitive lipase. Lipolysis can also be regulated over the longer term by changes in gene expression in response to growth hormone, cytokines, insulin, and glucose.
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Selected References
Botion LM, Green A. Long-term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose. Diabetes 1999;48:1691–1697.
Clifford GM, Londos C, Kraemer FB, Vernon RG, Yeaman SJ. Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes. J Biol Chem 2000;275:5011–5015.
Egan JJ, Greenberg AS, Chang M-K, Wek SA, Moos MC Jr, Londos C. Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet. Proc Natl Acad Sci USA 1992;89:8537–8541.
Eriksson H, Ridderstråle M, Degerman E, et al. Evidence for the key role of the adipocyte cGMP-inhibited cAMP phosphodiesterase in the antilipolytic action of insulin. Biochim Biophys Acta 1995;1266: 101–107.
Gasic S, Tian B, Green A. Tumor necrosis factor-α stimulates lipolysis in adipocytes by decreasing Gi protein concentrations. J Biol Chem 1999;274:6770–6775.
Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J Biol Chem 1991;266:11,341–11,346.
Holm C, Osterlund T, Laurell H, Contreras JA. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr 2000;20:365–393.
Klein S, Luu K, Gasic S, Green A. Effect of weight loss on whole-body and cellular lipid metabolism in severely obese humans. Am J Physiol 1996;270(Endocrinol Metab 33):E739–E745.
Kraemer FB, Shen WJ. Hormone-sensitive lipase: control of intracellular tri-(di-) acylglycerol and cholesteryl ester hydrolysis. J Lipid Res 2002;43:1585–1594.
Large V, Arner P. Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab 1998;24:409–418.
Londos C, Brasaemle DL, Schultz CJ, et al. On the control of lipolysis in adipocytes. Ann NY Acad Sci 1999;892:155–168.
Manganiello VC, Degerman E, Smith CJ, Vasta V, Tornqvist H, Belfrage P. Mechanisms for activation of the rat adipocyte particulate cyclic GMP inhibited cyclic AMP phosphodiesterase and its importance in the antilipolytic action of insulin. Adv Second Messenger Phosphoprotein Res 1992;25:147–164.
Okazaki H, Osuga J, Tamura Y, et al. Lipolysis in the absence of hormone sensitive lipase-evidence for a common mechanism regulating distinct lipases. Diabetes 2002;51:3368–3375.
Rahn T, Ridderstråle M, Tornqvist H, et al. Essential role of phos phatidylinositol 3-kinase in insulin-induced activation and phospho rylation of the cGMP-inhibited cAMP phosphodiesterase in rat adipocytes: studies using the selective inhibitor wortmannin. FEBS Lett 1994;350:314–318.
Ruan H, Miles PDG, Ladd CM, et al. Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-α: implications for insulin resistance. Diabetes 2002;51: 3176–3188.
Rydén M, Dicker A, Van Hermelen V, et al. Mapping of early signaling events in tumor necrosis factor-α-mediated lipolysis in human fat cells. J Biol Chem 2002;277:1085-1091.
Sengenès C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J 2000;14:1345–1351.
Sennitt MV, Kaumann AJ, Molenaar P, et al. The contribution of classical (β1/2-) and atypical β-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel β3-adrenoceptor agonists of differing selectivities. J Pharmacol ExpTher 1998;285:1084–1095.
Smih F, Rouet P, Lucas S, et al. Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose. Diabetes 2002;51:293–300.
Souza SC, De Vargas LM, Yamamoto MT, et al. Overexpression of perilipin A and B blocks the ability of tumor necrosis factor α to increase lipolysis in 3T3-L1 adipocytes. J Biol Chem 1998;273: 24,665–24,669.
Tansey JT, Sztalryd C, Gruia-Gray J, et al. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci USA 2001;98:6494–6499.
Wolfe RR, Klein S. Assessment of the control of the triglyceride/fatty acid cycle. In: Stable Isotopes in Paediatric Nutritional and Metabolic Research. Andover, Hampshire, UK: Intercept Ltd., 1987; pp. 115–122.
Yip RG, Goodman HM. Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density membrane fractions. Endocrinology 1999;140:1219–1227.
Zhang HH, Halbleib M, Ahmad F, Manganiello VC, Greenberg AS. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 2002;51: 2929–2935.
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Green, A. (2006). Cellular Regulation of Lipolysis. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_48
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DOI: https://doi.org/10.1007/978-1-59259-963-9_48
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