Regulation of leptin production: sympathetic nervous system interactions
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- Rayner, D. & Trayhurn, P. J Mol Med (2001) 79: 8. doi:10.1007/s001090100198
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Leptin is secreted primarily from white adipose tissue and stimulates long-form OB-Rb receptors in the hypothalamus to decrease food intake and increase energy expenditure. A variety of neuropeptides are involved in these responses, including neuropeptide Y, agouti-related protein, the prepro-melanocortin system and cocaine- and amphetamine-regulated transcript. OB-Rb receptors (and other receptor isoforms) are also found in peripheral tissues. Leptin is now known to have a wide range of peripheral actions and is involved in activating the immune system, haematopoiesis, angiogenesis and as a growth factor, as well as being a regulator of many cellular functions. The identification of leptin has led to reappraisal of the role of white adipose tissue from being an organ concerned primarily with energy storage as fat to an understanding that it is also a major endocrine and secretory organ. While the importance of the sympathetic nervous system in mobilising fatty acids from adipose tissue has long been known, it has become apparent that the sympathetic system is a key regulator of leptin production in white adipose tissue as well. Sympathomimetic amines and cold exposure or fasting (which lead to sympathetic stimulation of white fat), decrease leptin gene expression in the tissue and leptin production. On the other hand, sympathetic blockade often increases circulating leptin and leptin gene expression, and it is possible that the sympathetic system has a tonic inhibitory action on leptin synthesis. Apart from the few instances where leptin is absent, leptin levels are increased in obesity, while the sympathetic sensitivity of adipose tissue is reduced, consistent with the high leptin levels that are seen. The dysregulation of energy balance leading to obesity may partly involve a decrease in leptin sensitivity, or the leptin system may be set to have maximal effects at low leptin levels.