The Genetics of Obesity: Are You Destined to Be Fat?

Obesity and Genetics in lineThe entire premise of the Primal Blueprint is enabling you to be the architect of your health and happiness. If we can identify the environmental triggers and selective pressures under which the human genome developed, we’ll have a great roadmap for engineering our optimal lifestyle. And for the most part, it works. Not everyone will get the exact body they desire. You won’t all lose every extra pound. I can’t guarantee a six pack or a complete eradication of baby weight. But all in all, eating and living this way seems to produce good results. You can, it seems, affect your health, body composition, and fitness.

But genes still matter. And there’s a large trove of evidence showing that a person’s genetics are really good at predicting their risk of obesity.

A 1990 study took 12 pairs of adult male identical twins—with identical genes—determined their base metabolic rates and calorie needs, then overfed them by 1000 calories per day, six days a week for 12 weeks. Mean weight gain was 8.1 kg, ranging between 4.3 to 13.3 kg—all over the board, except for within the pairs of twins. When you compared one twin pair to another, weight gain was very different. When you compared twins within a pair, the weight gain was extremely similar. Not only that, but twins within a pair showed remarkable similarity in where fat was deposited (belly, hips, etc) and how much body fat was actually accrued. Overall, there was three times more variance in the various obesity measures between pairs than within them.

Genes explain how two people can have a vastly different responses to the same number of calories. They also explain how two twins can have the same response, and how two family members can have a similar response.

Subsequent papers have confirmed that obesity is highly heritable and that most of the heritability comes down to genetic factors.

How does it all work, exactly? What are these genetic variants doing that predispose us to obesity?

We don’t know most of them. Genome-wide association studies (GWAS), where vast reams of a population’s genetic data are analyzed to find patterns and associations between health conditions and genetic variants, can only point to genetic regions, not specific polymorphisms. Here are some specific ones, though:

Insulin resistance: The PTP-1B regulates insulin signaling, and polymorphisms to the gene have been shown to protect mice from otherwise obesogenic high-fat/high-sugar diets. Deletion of the gene protects mice against insulin resistance and diet-induced obesity, while mice with the full homozygous set easily gain weight. Another genetic variant increases insulin resistance by way of hypersensitivity to stress hormones. Folks with the variation tend to have more insulin resistance, higher body weights, larger waists, and a greater risk of type 2 diabetes.

Leptin signaling: Leptin affects bodyweight by regulating both satiety (increases it) and energy expenditure (increases it). If you have low leptin levels, or your leptin receptors aren’t responding to the hormone, you’ll likely eat more and burn less. Homozygous mutations to the leptin receptor gene which truncate its structure and inhibit its ability to interact with leptin increase the risk of obesity in humans. People with a genetic inability to produce leptin grow massively obese; supplementary leptin makes them lean.

Basal metabolic rate: BMR determines your baseline energy requirements—the number of calories you’ll burn just sitting around maintaining normal physiological function. Higher BMRs protect against obesity, while lower BMRs predispose you to it. That jerk who can sit around eating entire pizzas all day and stay lean? He’s probably got a high basal metabolic rate, which he got from his parents. Studies show that some portion of the obese population have a genetic variant that reduces their metabolic rate.

Hypothalamus signaling: The hypothalamus is the seat of obesity in the brain. It controls energy balance. It’s where the rewarding properties of food are determined. It’s where satiety and hunger originate. It’s riddled with leptin receptors that ultimately decide how much food we eat. And certain polymorphisms of the genes that regulate production of the compounds the hypothalamus uses to communicate and enact these decisions predispose us to obesity. Major polymorphisms to these genes are rare but almost always lead to severe obesity, while more minor variants may nudge us toward higher body weights.

Circadian rhythm: Polymorphisms in circadian rhythm genes can predict how a person’s energy expenditure will change in response to diets. If you’ve got the variant that causes a huge drop in energy expenditure when you diet, you’ll be less successful, more likely to eat extra food to compensate for the lost energy, and more susceptible to the negative side effects of calorie restriction (fatigue, malaise).

The tendency of most diets to fail also supports the primacy of genetics.

For most people, dieting just doesn’t work. They’ll lose weight, but gain it all back within a year. They’ll lose weight, and only keep it off if they subject themselves to ever-lower calorie counts that produce other unwanted health effects. They’ll keep it off as long as they have a team of clinicians hovering over them. In the real world, dieting to lose weight usually fails. If genes determine obesity, we’d expect this to happen.

Twin and adoption studies (where researchers see whether adopted children inherit their biological parents’ or adopted parents’ bodyweight) agree that obesity and being overweight are highly genetic. Overall, about 40-70% of obesity is hereditary. That sounds like a lot. That sounds like genes are your destiny.

But not everyone fails at their diets, do they?

We have hundreds of Success Stories right here on the blog that defy that claim. Many, maybe most of them are dealing with genetic propensities toward obesity, yet they figured out how to beat the odds.

Insulin resistant because of your genetics? Maybe a low-carb diet will work best for you. You can also lift heavy things, sprint sometimes, walk a ton, and do other things that improve insulin sensitivity.

Circadian rhythm gene polymorphism making you more sensitive to obesity-inducing effects of sleep deprivation? Get your sleep hygiene under control.

Basal metabolic rate lower than you’d like? It’ll be hard, but you’ll have to figure out a diet that inadvertently reduces caloric consumption.

These aren’t silver bullets. Swimming upstream against your own genetics is hard, and many, maybe most, people fail. But you don’t have to.

And another wrinkle in all this is that genes affect behavior. Got enough willpower to stick to your diet? It’s probably genetic. Open minded enough to consider that everything you’ve ever learned about health and nutrition is wrong and perhaps this Mark Sisson guy is onto something? You got it from your parents.

So yes: genes play a huge role in obesity.

Only genes can’t wholly explain the huge rise in obesity rates because genes don’t change that fast. People aren’t suffering from in vivo mutations to their “obesity genes” en masse.

The real problem is that almost everyone in the western world exists in a shared food environment which is obesogenic. If you live in America, you’re awash in drive-thrus, Big Gulps, and inexpensive, delicious processed food that’s been engineered to interact with the pleasure centers in your brain. Most modern countries are in similar boats, and obesity rates are climbing across other nations as they adopt our food-ways and work habits. The genes aren’t changing (at least, not quick enough to account for the stats).

The environment is changing. But because the environment has changed for everyone, and most people never really question its obesogenic nature—they eat the pizza, they buy the processed food, they sit for eight hours a day at work and watch TV for four, they slog away on the treadmill—researchers looking for the genetic origins of obesity miss or discount the effect of environment. Almost everyone whose genetic data they’re examining is exposed to the same obesogenic food environment, and its ubiquity masks its effects. The result is researchers pointing the biggest finger at genes. They’re not even “wrong.” The genes still play the major role.

Their mistake is assuming the environmental conditions cannot be changed. But they can.

Few researchers and genetic determinists consider the outliers, the ones who extricate themselves from the yoke of the yolkless omelets. The ones who read nutrition blogs and buy ancestral health books, and only use mayo made with avocado oil. They exist in the modern environment but resist its pull. They may have the genes for obesity but manage to remain—or get—lean. These are our people.

Genetic determinists might say that everything we’ll ever do is ordained by our genes. If we gain weight, it’s our genes. If we want to lose weight, our genes will determine how we choose to do it. If we choose to diet, our genes determine the best one, how our body responds, and how strict we are. If our body responds poorly, our genes determine whether we’ll give up or try something new. If we decide to start lifting weights, our genes determine whether it has any effect. And because we “can’t change the environment,” nor can we opt out of eating junk food or decide to drink water instead of soda if our genes won’t allow it, genes are all that matter.

That’s malarky.

You can view everything through the prism of genetics and heredity, but why?

I’m not even saying they’re wrong. Genes really do determine many things, including metabolism, behavior, and body weight. I just don’t see the point of thinking like that. Even if agency is an illusion, and I didn’t actually decide to pattern my eating and exercising habits around an evolutionary, ancestral blueprint but instead was ordained by my genes to do it, it’s a helpful one that I think we need to believe in.

Maybe belief in free will is genetically determined. I don’t know.

But I know that some people have figured out how to lose weight and keep it off in the modern obesogenic food environment. Have you?

Thanks for reading, everyone. Take care and be sure to leave your thoughts down below. I’m really curious to hear what you all have to say.

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About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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31 thoughts on “The Genetics of Obesity: Are You Destined to Be Fat?”

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  1. Great article, Mark. I like the takeaway. Reducing life to genetic determinism doesn’t do any of us any favors. So why buy into it (even if it were true)?

  2. Wow, lots of food for thought here. And it doesn’t really surprise me that genetics has such a big effect. After all, I can’t change my bone structure or my eye color no matter what I eat. But I wholeheartedly believe that everyone can improve the composition of their body by improving what they are putting into it. And aftee you improve the quality of you food, and see results, you start wanting to improve more things…your relationships, your living environment, your career…even your thoughts.

    1. Yep. “Destined” is a pretty carved-in-stone word. It leads one to believe that they have no control over their body weight and might as well just give up and go with an unhealthy flow. I think “tendency” would be more appropriate. Inherited tendency or not, obesity still boils down to what and how much a person eats or drinks. There is absolutely NO OTHER WAY to put fat on the human skeleton.

      Medications get blamed a lot, but I don’t buy it. They have no caloric value; they can, however, slow the body’s fat-burning mechanisms enough to cause weight gain unless food intake is adjusted accordingly. Knowing why you have a tendency to easily become heavy–and then have trouble losing it–is important so that the appropriate adjustments can be made. This is assuming one is willing to make those adjustments and knows how to go about doing it. MDA is an invaluable resource in that department.

  3. GREAT article. With obsogenic environments abound, it’s a little too quick for people to bank on genetics as the ultimate cause of obesity. Yes, like you pointed out, there are definitely people more prone to putting on weight and keeping it on. No doubt about that. But put one person in an obsogenic environment and the other in a healthy one, and you’ll have two different people.

  4. Great article. On an individual basis, we’ll never know which part of our health issues (weight, insulin resistance, etc.) are genetic and which part are environmental unless we are willing to throw out everything we “know” about nutrition and start over. It’s much easier to look around at our family members with similar body types/health conditions and blame genetics.

  5. I find that blaming my genes is way easier than blaming (and skipping) the IPAs.

    Maybe that’s just me, though…

  6. As genes play such a huge role in body size, I believe it’s important to focus more on health than weight loss. As Mary Roach pointed out in her book about space, your weight is simply a reflection of how strongly gravity is pulling on you. Health, on the other hand, determines quality of life. I know people of many different sizes that are leading happy and healthy lives. While our genetics may play a role in the pant sizes we wear, we have control on the habits and routines that shape our healthy lives.

  7. I had no idea genetics played such a large role- but I agree, it really shouldn’t stop you from achieving your health.

  8. Always knew my “genes” for the tendency to eat more than needed were going to be my biggest challenge. Very encouraging to be reminded that we do have more control than we are led to believe if we just give it a try.

  9. Having genetic predisposition of obesity definitely has its challenges, but I have many friends who have that makeup and still maintain healthy weight. Their support system (family and friends) was strong and helpful in their quest towards a healthy lifestyle. I feel fortunate to have grown up eating homemade healthy meals. And I have always been lean and been able to eat just about anything my whole life. However, I choose to maintain the healthy choices my parents had past onto me. And its paid off. Great article.

    1. “And I have always been lean and been able to eat just about anything my whole life.”

      Yes yes … you have mentioned that a number of times.

      1. I’ve been accused of that my whole life ( you can eat anything you want, blah, blah, blah) but what they don’t see is that I don’t eat whatever I want and I have both genetic predispositions and deliberate habits to keep me on track.

        I’ve never met a lean adult who “eats whatever they want” and still maintains leanness and optimal health. When I watch what they eat they either have naturally highly regulated appetites and a natural aversion to junk food – or – they regulate by habit – but it’s so ingrained it appears invisible to everyone else.

        To claim to eat whatever you want, or to be accused of it, doesn’t do anyone a service because it’s not true and puts health and fitness in the realm of magic or destiny.

        It would be like saying “I never make plans, set goals, look at a watch, or make appointments”….I’m just naturally on time and genetically gifted goal achiever.

  10. I like how you laid out all of the obstacles that people face. There are many and they are difficult to overcome. But you also make it very clear that genetics only pose a threat if you allow your environment to control them. This website and other sources of information to combat their predisposition towards obesity are readily available. It’s as much as decision as much as it is genetics.

  11. excellent article. genetics certainly plays a role that many don’t realize, yes, but here is the key

    “Their mistake is assuming the environmental conditions cannot be changed. But they can.”

    the effects of environment simply cannot be overstated.

    1. While I really enjoyed this article on a much more profound level, that was EASILY my favorite line.

  12. Olympic swimmers, gymnasts, and shot-put throwers all have different body types. However they still must fuel themselves correctly for peak performance. I will never have a runners body and I don’t want one. Diet is still the best medicine for health regardless of what our genes delt us.

  13. I have a crazy history of diabetes on the maternal side of my family and a lot of the research I do about food revolves around trying to figure out what contributed to my great-grandmother, my grandmother, and my mother all gaining weight starting in their late 30’s-40’s and keeping it until dying of some complications from diabetes (though my mom didn’t make it that far and died from pancreatic cancer at 45). My great-grandparents both had diabetes and lost toes, went nearly blind, and had practically every other complication. They were active people who worked a farm and a printing press, so activity level wasn’t their problem. Their diets were all home-cooked, but I imagine it included a lot of bread and potatoes. I have to say that watching all this happen in my family, the cupcake doesn’t look so sweet any more! However we shake the genetic dice, tossing sugar on the fire doesn’t seem like a sound idea.

  14. Very interesting! I agree that genetics can give us a tendency but don’t determine everything. I think you need to listen to your body and live the most healthy life you can. The ingredients of that might be different for different individuals.

    My parents are both very interested in their health (although, not primal). My mum fasts, lifts weights and does yoga; my dad fasts, is very active, interested in nutrition and teaches t’ai chi. I’m not sure if I’m open-minded from genetics or environment! But I’m glad I am.

  15. I can attest to environment. I am the only person within a healthy weight range in my family. Everyone else is obese. They eat a lot of starchy carbs, pizza, beer potaoes giant mexican platters, sugary sodas and desserts.. They actually seem to hate my daughter and I for not being overweight. Its all about what i put in my mouth. Some of its exercise but mostly about the food. So yes i think environment plays a bigger role than we think

  16. This sort of explains why a guy who lives a couple of houses away from me can drink like a fish (chronic alcoholic) and stay as skinny as a rail–no beer belly whatsoever. His mother was a large woman, and his father was average build, and neither of them drank.

    Of course, if this guy would actually eat FOOD, there might be a different story…

  17. A low carb high fat diet does not work for everyone with insulin resistance. You see, according to my genetic data, I put on weight on saturated fat. Which is evident from the fact that while the Primal diet made me asymptomatic on a lot of things, it hasn’t helped me lose weight at all. These days, I use a high-raw vegetarian Paleo-pescetarian diet to get around the problem. Still Paleo, but without the land meat or a lot of saturated fat.

    1. I am in the same boat. I have done one of those nutrigenomic diet tests and it came back I lose weight on a low fat /high complex carb diet. I also have some mutations that affect satiety, which in part explains why fat does not whet my appetite. I just want more. Eating a diet including grassfed beef/coconut oil/butter/nuts/dark chocolate diet did not work for me, I gained weight.

      But a diet of tubers, low carb veggies, beans and fish seems to work way better, at least for my blood sugar and weight.

  18. They call me patien zero because I’m okay with waiting and no one thinks I’m cool. I swear I don’t have AIDS.

  19. My question is what type of testing is available as an adopted 50 year old male ?

    I have to believe if the DNA can be tested our body composition must have certain elements that can give us the true primal blueprint.

  20. Yes, genetics play a large role in “…genetic propensities toward obesity”, but they really are not the final answer. My grandfather was fat, my dad was fat, I was fat (big boned 🙂 ), that was 140 lbs ago. In my N-1, diet and lifestyle trumped genetics. Now to see what it can do for male pattern baldness 🙂

  21. Awesome article as usual… Awesome read!
    Next TOPIC if you would please. .. Please expound on EPIGENETICS! That through food one can turn ON and OFF Gene expressions…specially the Obesity Gene. Thanks a lot.

  22. Re: Adoption studies — this is misleading. The adoptions in those studies are primarily of blended families adopting their spouses kids making the “nurture” aspect way more the cause not some magical predisposition to obesity.

    Diets don’t work. Lifestyle changes do — but that still involves CICO ,especially for people with disordered eating who have faulty hunger/satiation cues.

  23. Like everything, there are exceptions. What if you have SNPs that indicate likelihood of lack of adequate enzymes for digesting saturated fat and difficulty metabolizing saturated fat? Then a high fat diet which is high in saturated fat will make you sick, not healthy.

    Yes, one can take digestive enzymes, ox bile, and betaine hcl but there is no easy way to know how much to take. After years of experiencing sudden spikes in blood pressure to stroke range, I have finally figured out it happens when I eat too much (for me) saturated fat. Bacon and eggs, bulletproof coffee, and a big steak for dinner make my BP skyrocket. Plus gives me heartburn, inflammation, and assorted other problems.

    I would love to see an indepth article on genetics and obesity, but this article wasn’t it.

  24. This might be a dumb question, but it seems like knowing which genetic disadvantage you have is very important. How does one tell if your BMR or Leptin levels are low; if you’re insulin resistant? And once you figure that out, are there certain things you can do to counteract those conditions?