What is Melanotan II?

Melanotan II is a synthetic peptide shown to have many positive effects on body composition and energy homeostasis. The compound has many similarities to the peptide hormone 𝛼-melanocyte-stimulating hormone. By mimicking the effects of melanocortin peptides, not only does the compound play a role in energy homeostasis, but it primarily aids in increasing pigmentation of the skin. Due to this action melanotan II is colloquially referred to as ‘the Barbie drug” [1]

 

Main Research Findings

1. When administered to juvenile rats, melanotan II elicits positive effects on the hypothalamic neurocircuitry system, as well as the homeostatic conditions of body weight, NPY expressions, and energy expenditure.

2. Melanotan II acts as an appetite suppressant; administration of the compound leads to a significant reduction in body weight without a drastic caloric deficit.

 

Selected Data

1. In a study conducted by Glavas et. Al, they examined the effects of melanotan II in juvenile rats on the hypothalamic neurocircuitry system and the resulting effects on homeostasis such as body weight, NPY expression, and energy expenditure. Juvenile rats were injected twice daily at 0900 and 1700 with 3 mg/kg of melanotan II either 5-6 days postnatal, 10-11 days postnatal, or 15-16 days postnatal. Following injection the researchers determined the effects on stomach weight and brown adipose tissue uncoupling protein 1. Additionally, the researchers examined the effects injection of melanotan II had on NPY mRNA expression after twice daily injections from postnatal days 5-10 and 10-15 as well as the effects the treatment had on the activation of the central c-Fos gene which was tested 90 minutes after injection of melanotan II [2].

2. The subjects used for this study were six-month-old male F344BN rats, originally obtained from the National Institute on Aging Colony at Charles River Laboratories. The rats were placed under typical laboratory conditions and given a week to acclimate, they were then split into groups to receive a “low dose” of 0.04 μg/day of melanotan II or a “high dose” of 1 μg/day. The testing period took place over the course of 40 days. Any changes in the rats body composition were measured by time-domain nuclear magnetic resonance (TD NMR), as well as through the collection of organ and muscle tissue [3].

 

Discussion

1. It was revealed that the hypothalamic neurocircuitry system does not develop until three weeks after birth. Furthermore, neuropeptide Y (NPY) and 𝛼-melanocyte-stimulating hormone (𝛼-MSH) fibers found in the hypothalamic arcuate nucleus do not send signals downstream until approximately two weeks after birth. However, in newborn rats the 𝛼-MSH fibers are present at birth as well as melanocortin receptors.

The study concluded that in newborn rats, the activation of the c-Fos gene worked to increase body weight, while at more advanced ages the treatment led to a decrease in body weight and an increase in uncoupling protein 1. This indicates that injection with melanotan II leads to a inhibition of food intake as well as an spike in energy expenditure in the rats before the hypothalamic neurocircuitry system is fully developed [2].

 

Figure 1: analysis of c-Fos positive cells in the hypothalamus

2. The research team reported that administration of melanotan II led to induced transient anorexia for approximately 5 days. It’s important to note that anorexia was promoted with the addition of voluntary wheel running (VWR). The subjects were then split into two groups in order to measure changes in food intake or body weight that could be potentially skewed by exercise. The study reported that there was no significant difference between the two groups.

After the initial reduction in appetite, the food intake of the experimental groups increased to the same amount as the rats in the control group, however, both the high dose and low dose groups were seen to have maintained a lower level of body weight despite the increase in calories. Additionally, both the melanotan II experimental groups were seen to have a lower level of adiposity than the rats in the control group. The research team came to the conclusion that supplementation of melanotan II can lead to a reduction in body mass without a drastic restriction in caloric intake [3].

 

Figure 2: changes in body mass and food intake based off the dosage of melanotan II given.

 

Conclusion

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

Citations

[1] Massy, Maddie. “What is Melanotan-II – the drug that the TGA urges consumers to avoid?” UNSW Newsroom, 30 January 2023, https://newsroom.unsw.edu.au/news/health/what-melanotan-ii-drug-tga-urges-consumers-avoid. Accessed 18 April 2023.

[2] Maria M. Glavas, Sandra E. Joachim, Shin J. Draper, M. Susan Smith, Kevin L. Grove, Melanocortinergic Activation by Melanotan II Inhibits Feeding and Increases Uncoupling Protein 1 Messenger Ribonucleic Acid in the Developing Rat, Endocrinology, Volume 148, Issue 7, 1 July 2007, Pages 3279–3287, https://doi.org/10.1210/en.2007-0184

[3] Côté I, Sakarya Y, Kirichenko N, Morgan D, Carter CS, Tümer N, Scarpace PJ. Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction. Can J Physiol Pharmacol. 2017 Feb;95(2):206-214. doi: 10.1139/cjpp-2016-0290. Epub 2016 Oct 19. PMID: 28051332; PMCID: PMC5572812.