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    DNA: I Am Who I Am… or Am I? – Session Thirteen

    Overweight and Obesity – Is it Me, or My DNA?

    5HT2C and MC4R: Can Your Genes Make You Fat?

    “Genes influence form, function and fate, but these influences typically do not occur in a one-to-one manner.”

    – Siddhartha Mukherjee, M.D.

    “DNA+Evironment+Triggers+Chance = Your Biological Destiny. Prevent and heal overweight and obesity more effectively with a simple cheek swab that tests for the 5HT2C gene and MC4R gene.”

    – Bruce Alan Kehr, M.D.

    Reader, I don’t mean to be blunt, but have you gained a little weight lately? If you’re like the vast majority of Americans, I bet your answer is yes. Over a third of our population is designated as medically obese, but the specter of weight gain affects us all. The matter of weight gain or loss represents an interesting cross-section of our culture: We are collectively obsessed with our high beauty standards, and we are also obsessed with the idea of self-determination: that we have the power to effect change on every circumstance we find ourselves in, that through sheer force of will, we can be whoever we want to be. Naturally, we think very highly of those who have achieved the standard of beauty. We also think highly of those who exhibit “strong willpower” in their lives by taking control of their circumstances. Inversely, those who do not abide by the beauty standards can feel practically invisible in our society—and all too often, those who are seemingly unable to change their lives for the better are seen as “weak” or “less than”.

    As a psychiatrist, I often find myself working against these culturally determined belief systems—beliefs that are so ingrained we hardly think twice about them. Because in truth, beauty is subjective (and not uncommonly, outer beauty belies inner ugliness), and the issue of willpower is vastly complex. Now, I am a strong believer that we can all take control of our circumstances—in fact, I have a chapter in my new book about this very topic. Those who don’t believe they have control of their lives too often fall into a pattern of entitlement (things are “owed” to them) or learned helplessness (they “deserve” their circumstances or are powerless to change them). But here’s where I differ from many who hold so strongly to the pull-yourself-up-by-your-bootstraps mentality: in order to change your circumstances, you first have to acknowledge your constraints. The fact is, there are things outside of our control. Sometimes, those things are external to us: societal forces working against us and our pursuits that we must consider how to mitigate. Other times, those things are within us. In fact, our constraints can be written into our very genes. And for some of us, weight loss is not just a matter of sheer will and determination. Our genetic code has a lot more say than most of us think. Our DNA, in this sense, may be our number-one constraint. But that doesn’t mean we can’t still take action. The first step in taking control of our destiny is to understand what we’re working with, so we can build a more precise strategy to conquer that which holds us back and move on to achieve our dreams.

    Today, we’re going to talk about a pair of genes that can predispose us to weight gain. Let’s dig in!

    MC4R and Weight: Why MC4R Genetic Testing can be a Valuable Tool for Weight Loss

    Scientists understand quite a bit about our universe. They understand gravity, the speed of light, how planets are formed and stars are made. But there’s one key force that continues to mystify even the most brilliant of minds: dark matter: an unseen, mysterious force in the universe that has a sort of shadow influence on systems that have yet to be accounted for. Similarly, for years—decades even—the prevailing understanding around weight loss revolved around the calorie: if you take in more calories than you burn, you will gain weight…. and if you burn more calories than you consume, you will shed those pounds. And yet, when some followed the calories in, calories out strategy; their waistlines failed to shrink. Like dark matter,  there seemed to be a mysterious force that influenced weight gain and weight loss that somehow fell outside the usual and customary formula. We still don’t know what dark matter is, but we have solved the mystery behind one weight-loss force: the Melanocortin 4 Receptor, or MC4R.

    This gene does a significant amount of heavy lifting when it comes to our body weight. It regulates food intake (calories in), energy expenditure (calories out), and—importantly—satiety.  MC4R does so through two signals: anorexigenic peptide signals promote the feeling of fullness (known as “satiety”) that keeps us from eating more than we need. Orexigenic peptide signals promote the feelings of hunger and help our bodies store the calories we give it. It’s easy to see, given those straightforward mechanisms, how a variation on this gene may alter those signals and distort them. In fact, receptor desensitization—that is, signaling that is weakened or otherwise has gone awry—can lead to feelings of hunger even when a full meal has been consumed, it can lead to storage of calories the body does not need, and it can lead to a lessened energy expenditure overall. Here’s an image that depicts this concept:

    5HT2C-and-MC4R-content-photo-1Many overweight people eat normal amounts of food, but their bodies store it in a way that makes it more difficult to burn off. Others feel hungry more frequently. Neither of these mechanisms are within our control—and the assumption that they  can be controlled is devastating to an individual’s self confidence and body image. “If only I had enough willpower to make change” just doesn’t work when your cellular DNA is working against your goals. Taking an MC4R genetic test can shed light on that misunderstanding and help you develop more proactive solutions for weight loss.

    5HT2C: Serotonin, Antipsychotics, and why 5HT2C Genetic Testing Works

    5HT2C is the abbreviation for Serotonin Receptor Subtype 2C. Serotonin, as we have discussed previously in this series, is a neurotransmitter that plays a number of roles within our body—from digestion to appetite control to mood regulation. This gene does its work in a part of the brain called the hypothalamus, which also regulates food intake and appetite. On its own, this gene can lead to predispositions of weight gain or weight loss through increased or decreased levels of serotonin. However, 5HT2C is also directly affected by certain medications that can directly cause obesity in those with a specific variation.

    In a previous blog, we discussed DRD2: the single gene that codes for the D2 receptor on the surface of brain cells, which is targeted by the vast majority of antipsychotic medications. Antipsychotic drugs regulate levels of dopamine in the brain—too much of this neurotransmitter can contribute to schizophrenic and manic episodes. However this class of drugs also has a direct impact on 5HT2C: atypical antipsychotics are 5HT2C antagonists, meaning they block 5HT2C receptors. For those with a specific genetic variant of 5HT2C, this can lead to mixed hunger/satiety signals, and reduced abilities to feel full after a meal as well as an increase appetite. And yet, while many patients with bipolar disorder, treatment resistant depression, and schizophrenia desperately need atypical antipsychotics to feel better and function more effectively; significant weight gain will not only worsen their self-esteem, it will contribute to many other health problems that come from being overweight, including metabolic syndrome (pre-diabetes insulin resistance, high blood pressure, high cholesterol). Well, what’s a psychiatrist to do?! Fortunately, there is a wonderful medication on the market that treats this genetic variant and prevents weight gain in patients that need these medications. It is called Belviq (lorcaserin) and it works by directly stimulating the 5HT2C receptor to make you feel full! Here is a picture of how it works in the brain:


    A 5HT2C genetic test can determine if you have the variant that would be affected by certain antipsychotic drugs and lead to weight gain, and if you are therefore a candidate to take Belviq to prevent weight loss.

    Conclusion: Take Control of Your Genes by Learning More About Them

    Assuming that weight gain is always due to weak willpower is simply never the full story—and often it’s not even part of the picture. Genes play a major role in the regulation of hunger and feeling-full, and genetic testing can determine whether or not you’re predisposed to weight gain, and whether you should steer clear of certain antipsychotic medications, or take an antidote medication if you must have them.

    You can take control of your DNA and your destiny—but first it would help to understand your constraints. Take a genetic test today to find out how your body works (or doesn’t work so well) for you—and how you can work to improve your body’s health.


    DNA: I Am Who I Am… or Am I? Blog Series

    1. Does DNA Determine My Destiny?
    2. Tinker with Your Genes to Determine Your Destiny
    3. A Simple Cheek Swab Brings Good Karma
    4. Test Your DNA to Determine Your Reality
    5. The BDNF Gene: Use “Fertilizer” to Grow a Majestic ”Rainforest Brain”… and Introducing “GENiE” and “DNA 4 KIDS”
    6. The MTHFR Gene: “Manufacture” Your Way to Health and Happiness Featuring “DNA 4 KIDS” with “GENiE”
    7. The SLC6A4 Gene (Serotonin Reuptake Gene): Improve Your Mood and Anxiety through a Simple Cheek Swab Featuring “DNA 4 KIDS” with “GENiE”
    8. Tame that Emotional Roller Coaster Ride Genetic Testing for the ANK3 Gene and CACNA1C Gene Featuring “DNA 4 KIDS” with “GENiE”
    9. Is Addiction Inherited? Genetic Testing for the OPRM1 Gene, Opioid Abuse, and Alcoholism Featuring “DNA 4 TEENS” With “GENiE”
    10. Surf’s Up: Use Your Genetic Code to Ride the Stress Wave with Ease The COMT Gene Featuring “DNA 4 KIDS” With “GENiE”
    11. Mental Illness is not a Myth—and Human Genomics Proves It The DRD2 Gene and Dopamine Featuring “DNA 4 KIDS” With “GENiE”
    12. ADHD in the Age of Distraction The Tricky Genetics behind ADHD and ADRA2A Featuring “DNA 4 KIDS” With “GENiE”
    13. Overweight and Obesity – Is it Me, or My DNA? 5HT2C and MC4R: Can Your Genes Make You Fat?
    14. Is Alcoholism Inherited? Can a Tiny Gene Help Treat It? The GRIK1 Gene
    15. 2018 Women’s Health and Wellness Summit DNA Keynote Address


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