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 Melanocortin System and Obesity 
The following is one in an ongoing series of columns entitled What Will Work for Me? by . View all columns in series
Competency: Weight Loss and Weight Control

You can’t just dive in and lose weight? Having trouble with being a little overweight? It seems so simple. Eat less and exercise more! Well, not so easy. Which is why we are all getting fatter. Have you ever heard of the melanocortin system? I hadn’t.

One tiny column is hardly enough to teach you much, but it’s an idea you need to know about, even if just in name. Let me give this a try. Your brain makes a large protein called pro-opiomelanocortin or POMC for short. It can be broken down into 7 different shorter pieces, all called collectively the Melanocortins, hence the melanocortin system. One is called endorphin (your natural opioid). That deals with pleasure and pain. Another is melanocortin with stimulates melanocytes. That is all about skin and hair color. But it is also complex because they can stimulate appetite, blood pressure, inflammation, skin and hair pigmentation and bone growth. Whew. And then there is ACTH, another of the 7 peptides that come from POMC. It stimulates the production of cortisol. Finally, there is lipotropin that is all about fat. And here is where we spin off into leptin and its feedback loops with serotonin and first and second order neurons giving varying levels of feedback. Confused yet? The reason this matters is that we are beginning to understand and make the connections between why women gain weight around menopause and just can’t lose it for the life of them. It sticks like glue. Unless you mess around with the opioid suppressor system. And if you have polycystic ovarian syndrome, this is all about you.

What’s that? Naltrexone is an opioid blocker and low dose naltrexone is one of the first coarse methodologies discovered that works with blocking the dysfunctional aspects of the melanocortin system. Haven’t you ever felt like eating was an addiction and you just couldn’t stop? Can you imagine what your brain is saying when you are 8 scoops into the ice cream bucket? (YES!!!) What we find in the second paper is what happens when women start losing their estradiol with menopause. In the brain, estradiol is used to enhance the expression of POMC. As it drops out of the picture, fat mass increases as a way to make more estradiol via the enzyme aromatase that happens to be in fat tissue. You gain weight to make more estradiol. And that makes your brain happy. Wouldn’t it be easier to just give you a wee bit of estradiol….just a smidgen?

Now, interestingly enough, if you want to lose weight, you can take low dose naltrexone and bupropion and you don’t level out because you have blocked the endorphin negative feedback effect.

WWW. What will work for me? This is one of those way-over-the-top ideas I’m trying to get my head around. But it may be the beginning of a larger conversation. The road to successful weight loss may be around this corner. Certainly we are seeing that low dose naltrexone works with weight loss in some overweight folks, particularly if they have Polycystic ovarian syndrome. As for me, I’m just a hunkering down and trying to focus on having an apple instead of ice cream for my bedtime snack. My endorphins would be happier if I had the ice cream.

Reference: Biochem J 2010 May 27;428(3):305-24 and Eur J Pharmacol Jun 2011 June 11;660(1)1;181-7

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 About The Author
John Whitcomb, MD is a wellness physician based in Milwaukee. His board certification in Anti Aging and Regenerative Medicine, Holistic and Integrative Medicine and Internal Medicine puts his insight at the point of......moreJohn Whitcomb
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