Reduction of Orexigenic and Adipogenic Effects of Neuropeptide Y

Melanotan II or Melanotan 2 is a synthetic analog of the melanocortin peptide hormone that naturally occurs in the body. It was developed for research into melanogenesis, a condition that causes the skin to develop this chemical improperly. Since then, a number of clinical trials have been developed to explore additional uses for this chemical as well as the potential dangers of exposing humans to this product.

There are numerous counterfeit versions of this chemical available on the market today. Many of these are sold under the name melanotan I and II. To days, no product that contains melanotaon II has been approved for human use by the FDA, so any products that claim to incorporate this chemical are not telling the truth or working with counterfeit products.

Neruopeptide Y acts as a strong orexigenic neruortransmitter which may also be referred to as aneurodocrine axes, or a-melanocyte stimulating hormone MSH.

This peptide may act as an essential anorectic neuropeptide which has an impact on hypothalamic receptor subtypes.

When it is applied as an intracerebroventricular bolus injection, the non-selective MC receptor antagonist melanotan 2 can suppress the NPY orexigenic action, inhibit feeding and reduce basal insulinaemia. Evaluating these effects throughout a 7 day trial with central infusions of melanotan 2 on its own oar alongside NYP in male Sprague-Dawley rats has revealed much about this functionality.

Once applied to these rats, melanotan 2 caused nearly full anorexia for the initial 1-2 days, but in spite of the continued infusions feeding returned on subsequent days.

When melanotan 2 was applied with NPY it produced similar anorectic behavior but then feeding reached normal levels that cancelled out the hyperphagia that NPY caused.

NPY infusions produced a fat pad weight while melanotan 2 reduced the adiposity in the rats and drove down the increase of fat pad weight developed from NPY applications. This peptide also curtailed insulin increases and leptin secretions that stemmed from exposure to NPY.

Characterization of Melanocortin Receptor Ligands

Melanocortin MC3 and melanocortin MC4 make up the primary subtypes of melanocortin receptors that are expressed in rat brains.

This activity was characterized by an affinity for nine melanocortine receptor ligands which were used by such receptors in vitro.

Their activity was also defined as ‘melanocortin induced behavior’ in the rat such as grooming behavior.

The potency of the receptor antagonists fit well with the potency of the ligands when stimulating the grooming behavior.

Applying a-MSH induced melanocortin activity while in vitro and induced grooming behavior was reintroduced throughout the experiment. Melanotan 2 was effective in inducing this behavior and increasing ligand potencies, along with such behavior.

Melanocortinergic Activation

Hypothalamic neurocircuitry regulating homeostasis in adult rats cannot be developed until the third postnatal week.

During this time fibers from hypothalamic arcuate nucleus innervate downstream to the necessary targets until the second postnatal week. However, a-MSH fibers from the melanocortin receptors and brainstem are present from birth.

Examining these effects against antagonists, such as melanotan 2, indicate how energy expenditure, body weight and hypothalamic NPY expression occur.

To demonstrate this, young rats were injected with melanotan 2 and their stomach weight was measured during a tissue uncoupling protein 1 mRNA examination.

Stomach weights were decreased while protein 1 mRNA was increased at all ages, following this experiment. This indicated that decreased food intake coupled with an increase in energy expenditure stems from applying melanotan 2.

Melanotan should not be used for human trials, though the FDA is beginning to approve early phase trials for this product. At this time the potential for side effects from exposure to the chemical places an undue risk on those that would participate in any such study.