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MT-2 (Melanotan-2) and Hunger

“product By Logan 6 months ago

It is has been known for some time that leptin regulates satiety, but the exact mechanism of regulation has remained elusive. Research has recently revealed that leptin and melanocortins affect the same brain regions associated with hunger and metabolism. This finding has led to new insights into both leptin physiology and the effects of melanocortin analogues like melanotan-2 (MT-2).

The Role of Leptin in Hunger

Leptin, which is made by fat cells, controls both food intake and energy expenditure. A large majority of its effects are mediated through proopiomelanocortin (POMC) neurons in the central nervous system. By stimulating POMC neurons, leptin creates feelings of fullness. In some individuals, a decreased sensitivity of POMC neurons to leptin has been linked to an inability to detect satiety[1].

How Melanotan-2 Fits

Animal studies of melanotan-2, a melanocortin receptor agonist and derivative of the naturally occurring alpha-melanocortin-stimulating factor (Alpha-MSF), have indicated that the hormone can reduce fat storage and reduce hunger. MT-2 activation of the melanocortin-4 receptor (MC-4R) has been found to alter food intake food preference in rodents. Animals with MC-4R deficiencies tend to prefer fatty foods and will consume as much as 95% more of a fatty meal than control animals will[2]. Those treated with MT-2 tend to avoid fatty foods and eat much less.

Careful research has demonstrated that MT-2 and leptin affect different aspects of the same nerve pathway. Alpha-MSF, the natural analogue of melanotan-2, is produced by POMC neurons and acts as a negative regulator of food intake[3]. Administration of leptin leads to melanocortin signaling, which leads to POMC activation. Thus, some of leptins effects are the result of its effects on melanocortin levels[4].

Exogenously administered leptin has never been a particularly effective treatment for obesity, even in those who are leptin deficient. The realization that melanocortin signaling is the mechanism by which leptin has its effects led to the discovery that there are both leptin-dependent and -independent melanocortin signaling systems. In other words, melanocortin works in conjunction with leptin to lower hunger, but it also works on its own. This breakthrough has been a major driver in the increase in clinical studies of melanotan-2 and its derivatives.


[1] H. Pan, J. Guo, and Z. Su, "Advances in understanding the interrelations between leptin resistance and obesity," Physiol. Behav., vol. 130, pp. 157-169, May 2014.

[2] A. van der Klaauw, J. Keogh, E. Henning, C. Stephenson, V. M. Trowse, P. Fletcher, and S. Farooqi, "Role of melanocortin signalling in the preference for dietary macronutrients in human beings," Lancet Lond. Engl., vol. 385 Suppl 1, p. S12, Feb. 2015.

[3] C. Bjørbaek and A. N. Hollenberg, "Leptin and melanocortin signaling in the hypothalamus," Vitam. Horm., vol. 65, pp. 281-311, 2002.

[4] H. Shimizu, K. Inoue, and M. Mori, "The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure," J. Endocrinol., vol. 193, no. 1, pp. 1-9, Apr. 2007.

Posted in: Melanotan II