Saturday, 12 April 2014

weight control with a MC4R agonist

I have to make another post about Melanotan-II ( mt2 )

About 3-4 weeks ago I started another course of mt2. I take 1mg per day ( I am skin type I, "only burns and never tans" probably due to a genetic defect in my MC1 receptor ) , 5 times per week. After 3 weeks everyone asks you "where" youve been on holiday, lawl.

I had forgotten how amazing this peptide is. I noticed instant changes when I started taking it, appetite went WAY down, bodyfat started to decrease, carb tolerance is up, urge to move went way up, I even found the energy and motivation to going to the gym again.

Infact its started to become glaringly obvious to me that weight control with a MC4R agonist is almost effortless. ALMOST! I can only imagine how wonderful leptin must be for reduced obese people, if im having this much of a good time on mt2.

.Feeling revitalized on mt2 I decided to go back and check the literature on this drug, and heres some interesting studies,,,,

Melanocortin receptors in leptin effects. - this study highlights the important point that Mc4R is essentially downstream of leptin, so much so that leptin doesnt work in ob/ob mice if you block MC4R.

Novel α-MSH analog causes weight loss in obese rats and minipigs and improves insulin sensitivity

Central effects induced by MTII following peripheral dosing - provides evidence that subc administration of mt2 can still cross the blood-brain barrier. This is important because a large portion of mt2's effects on bodyweight occur via central mechanisms.

The leptin-like effects of 3-d peripheral administration of a melanocortin agonist are more marked in genetically obese Zucker (fa/fa) than in lean rats. - Further evidence that MC4R is responsible for leptins effects on bodyweight.

Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues. - mt2 in the brain stimulates rapid mobilization of fat stores.

MTII administered peripherally reduces fat without invoking apoptosis in rats. - unlike leptin, Mc4R doesnt kill adipose tissue.

Intermittent MTII application evokes repeated anorexia and robust fat and weight loss. - the appetite reducing effects of mt2 wear off after about 1-2 weeks, I can confirm this, BUT bodyweight stays reduced.

Melanocortin receptors mediate leptin effects on feeding and body weight but not adipose apoptosis.

Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression.

Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet. - this is a very interesting study, it suggests that preference for dietary fat depends on Melanocortin signalling, such that if Melanocortin signalling is high, you DONT want to eat fat, AND your body is simultaneously burning fat.

Melanocortin activity in the amygdala controls appetite for dietary fat. - high melanocortin signalling = dont want to eat any fat.

Central administration of melanocortin agonist increased insulin sensitivity in diet-induced obese rats. - mt2 in the brain improves insulin sensitivity. I have yet to summon the evidence to prove this, but I have a hunch this is because central melanocortin increases fax oxidation within the adipocyte.

The central melanocortin system directly controls peripheral lipid metabolism. - important study, shows that a lack of melanocortin signalling in the brain causes 1) increased TAG synthesis in the liver 2) decreases glucose use by muscle 3) increases insulin sensitivity of adipose tissue 4) promotes TAG synthesis in WAT

So in short, when melanocortin signalling in the brain drops, you become hungry and want to eat dietary fat, AND simultaneously your body is actively shuttling all fat towards storage.

**Region-specific differences in brain melanocortin receptors in rats of the lean phenotype. - injection of MT-ii into the brain causes increased physical activity.

Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice.


  1. Do you have any concerns about negative side effects?
    Did you ever discuss Melanotan with Wooo? This would seem to be right up her alley although there are no references to Melanotan on her blog.

    1. Yes I have concerns about negative side affects, but I fully research a drug before I use it.

      The only "negative" side effect ive had with melanotan so far are new freckles that seem to be permanent since they did not disappear when I was off my first cycle for over 6 months. Some people get new moles on melanotan, for which I have been lucky not to get so far.

      I think its worth remembering Mt-ii was developed for people that have extreme difficulty tanning under normal sun exposure. If you tan easily, then mt-ii is not for you.

      The point of this post was not really to advocate MT-II, but rather highlight how important brain melanocortin signalling is in controlling fat mass. Not amount of dieting or exercise will make up for a low melanocortin tone in the SNS.


  2. Wooo has an odd reluctance to use anything hormonal except leptin itself, even though there are lots of things that might (likely would) help her; e.g. HGH (or releaser peptides), T3, melanotan. A little bit of mesterolone and some time in the gym would do wonders for her, too, in my poorly-informed and unsolicited opinion. :-)

    1. Oops. I said "mesterolone"; I meant oxandrolone (anavar). Less androgenicity.

    2. i think a dedicated mc4r agonist that works in the CNS would be a big help to everyone facing weight problems, especially dieted down people.

      melanotan II is not really viable for this because it is a very strong MC1R agonist and will make you go black as night if you use it frequently enough to reduce weight.

      you need an agonist that works primarily on mc4r

  3. Is this a prescription med? I can barely tan even after hours sunning.

    1. its an "underground" manufactured peptide. You need to order it from a website that normally deals with GH related peptides. Its quite easy to get in the UK. dont know about the US.