Is there an obesity gene?

When I first heard about the discovery of a potential obesity gene on the news, I ignored it. After all, a gene only codes for a single protein, and there are about 25,000 genes of which nearly 1,000 seem to be associated with obesity. Nonetheless, I decided to read the research paper in its pre-publication form (1). Even though it is an incredibly scientifically dense paper, rich in genetic jargon, it finally did it begin to make sense.

The protein for which the gene in question codes is called a transcription factor. Transcription factors are the key players in the process of transferring hormonal signals from the surface of the cell to ultimately generate the gene expression of new proteins. As I explained in my book, “Toxic Fat,” nuclear factor-κB (NF-κB) is the transcription factor that turns on the genetic expression of more proteins that leads to cellular inflammation (2).

The transcription factor in this article, known as KLF14, seems to be related to turning on the metabolic responses that lead to insulin resistance, obesity and metabolic syndrome.

Transcription factors have been around for hundreds of millions of years, and they have been highly conserved by evolution because they work so effectively to fine tune gene expression. This might be expected since they are the key players in turning genes “off” and “on” inside the cell. Since they have been around for a long time, this also means that there are natural compounds (usually nutrients) that are instrumental in controlling their activity. For NF-kB (the master regulatory switch for inflammation), it is known that leukotrienes derived from arachidonic acid activate this transcription factor (3,4), whereas omega-3 fatty acids and polyphenols inhibit its activation (5-7). It is very likely the same nutrients may do the same for the activity of the KLF14 transcription factor. From an evolutionary point of view this makes common sense since in less developed organisms (like the fruit fly), the control of fat, metabolism and immunity are found in a single organ known as fat bodies (8).

As I have pointed out in my books, increased cellular inflammation is the first step toward metabolic dysfunction. This is why any decrease in nutrients like omega-3 and polyphenols or any corresponding increase in nutrients like arachidonic acid may be common nutrient control points that dramatically influence our future health. Obviously, as the balance of these nutrients change, their effects on various transcription factors will amplify their impact on gene expression.

A more ominous implication from this study is that the gene mutations that gave rise to increased insulin resistance came only from the mother. This may be the link to understand how fetal programming transmits epigenetic information from one generation to the next. The combination of fetal programming with radical changes in the human diet may well prove to be a deadly combination for our future health and longevity.

References

  1. Small KS, Hedman AK, Grunberg E, Nica AC, Thorleissson G, Kong A, Thersteindottir U, Shin S-Y, Richards HB, soranzo N, Ahmadi KR, Lingren C, Stefansson K, Dermitzakis ET, Deloukas P, Spector TD, and Mcarthy MI. “Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.” Nature Genetics doi 10:1038/ng/833 (2011)
  2. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  3. Sears DD, Miles PD, Chapman J, Ofrecio JM, Almazan F, Thapar D, and Miller YI. “12/15-lipoxygenase is required for the early onset of high-fat, diet-induced adipose tissue inflammation and insulin resistance in mice.” PLoS One 4: e7250 (2009)
  4. Chakrabarti SK, Cole BK, Wen Y, Keller SR, and Nadler JL. “12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes.” Obesity 17: 1657-1663 (2009)
  5. Denys A, Hichami A, and Khan NA. “n-3 PUFAs modulate T-cell activation via protein kinase C-alpha and -epsilon and the NF-kappaB signaling pathway.” J Lipid Res 46: 752-758 (2005)
  6. Zwart SR, Pierson D, Mehta S, Gonda S, and Smith SM. “Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation.” J Bone Miner Res 25: 1049-1057 (2010)
  7. Romier B, Van De Walle J, During A, Larondelle Y, Schneider YJ. “Modulation of signaling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.” Br J Nutr 100: 542-551 (2008)
  8. Hotamisligil GS. “Inflammation and metabolic disorders.” Nature 444: 860-867 (2006)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

19 thoughts on “Is there an obesity gene?

  1. why was the amount of fat in the diet changed from the 1998 edition of your book, when the nutitional blocks were 7 protein, 9 carbs, and 1.5 fat grams?

  2. I tried to make it easy for the person to calculate total fat if they were weighing food items on a scale. For example, if the protein contains 10% fat, the one block of low-fat protein would also contain 1/2 block of fat.

    On the other hand, if you are looking at labels or using a computer to calculate the total calories, then one block of fat is the 3 grams

  3. Dr. Sears,
    You seem to be implying that genes come from the mother and the obesity gene starts in the womb but it is my assumption that genes come from your ancestry, just that they are passed on by the mother. And I don’t think that the concern about any obesity gene or blaming obesity on genes is nearly as important as concentrating on people developing self conrol and will power to counter any gene that might cause the person to become obese. People must learn to become responsible for their own actions and not be classified as victims of obesity beyond their own control. I believe in a conservative outlook and not a liberal one.

    • It’s about epigenetic programming taking place in the womb in which environmental factors (diet, stress, diabetes, etc) can imprint the genetic code of the developing fetus. Epigenetic programming continues during the post-natal phase. This is why the most rapidly growing group of obesity is in children under the age 4 well before the age they develop behavioral habits.

  4. But after the age of 4 or when they can adjust their own behavioral habits they can easily reverse their obesity so I don’t accept this obesity starts in the womb theory.
    Is it not true that, and can the reverse be said that, slimness or thinness also starts in the womb? And can a genetically thin person reverse their thinness and slimness by overeating and becoming obese. Yes they can.

  5. Hi Dr. Sears,

    I wonder where this leaves us? I mean does it mean if you have this obesity gene you automaticially will have problems with your weight? Is this a gene that can be altered?

    • It means that you will have to pay much closer attention to what you eat to prevent its expression. This means keeping cellular inflammation under control for a lifetime by following an anti-inflammatory diet. It can be done, it just takes constant dietary awareness.

  6. hi all, i would recommend reading ‘ the biology of belief ‘ by bruce lipton. This guy is a molecular biologist and his research shows that environmental stimuli far outweigh the influence of genetic
    factors.

  7. It occurs to me, that assuming some, or many, or most, or all of us have an obesity gene, still doesn’t alter the fact that a certain number of calories equal a pound of weight. So, even if a person was “inclined” to consume more calories than needed, they might also be able, through developing, by various means, self control, resist the urge to consume excessive calories.

    • If you have a genetic “fat trap” that I described in my latest book, Toxic Fat, the “calorie in, calorie out” thinking is no longer valid. Unless you reduce the cellular inflammation that is driving that fat trap, the only way to resist the physiological demand to consume excessive calories to make adequate levels of chemical energy (i.e. ATP) is always to be hungry and fatigued. It seems to me a more positive strategy is simply to reduce the cellular inflammation in the fat cells that is activating the fat trap in the first place.

  8. Dr Sears,

    I have thanked you before, but I will thank you again for all of your hard work and research over the last 20 years (at least) – following Zone “rules” I have put an end to the weight battle that is definitely a part of my family heritage. Your books are different from others in that you are always testing your theories in a highly scientific manner.

    Sometimes your theories have been way off (how can you forget the borage adventure?) and you go back to re-formulate. I am confident that you are dedicated to scientific proof – which brings me to the point of this message: I do not understand why you so often refer to evolution in your books and blog articles. It would not bother me if these statements, such as the one from this very article: “Transcription factors have been around for hundreds of millions of years, and they have been highly conserved by evolution because they work so effectively to fine tune gene expression.” were not confidently put forth as fact. You may 100% believe what you are saying, but that does not make it a fact.

    Well, I got that off my chest – I suppose there will be some backlash over what I wrote, but it has bothered me for quite awhile. It seems to me that what is important is how our bodies operate NOW, and how to be healthy in our present environment – throwing in all kinds of statements that begin with “thousands/millions/billions of years ago” does nothing to validate what is true TODAY.

    Just something to think about. Again I am very grateful to you for all you have done to help people lead long and healthy lives. Bravo!

  9. For what I can see there is a lot of “bargaining” been thrown around…
    Well, what can we say when evolutionary factors are what modify our bodies and have been modifying it for hundreds of millions of years, we are the result from an incredibly extensive yet simple “switch board”, our bodies, as any living entity’s on this planet, have been adapting to our ecosystem and as a part of this ecosystem we have developed into an organic form that has earned its right to prowl the earth.
    We continuously modify, every day, every hour, every minute of our life, our body in order to adapt to our medium, that is the reason for illnesses, gaining or shedding weight, the colour of our skin, the shape of our eyes, our hight, our built, all comes from adapting to our medium. Everything has been a painstaking process of “natural selection” that is greatly influenced by what we eat. Have you ever wondered why there has been a sudden explosion on violent allergies to food? Like peanuts, pecans, almonds, fish, starch, etc. All comes from processed foods, specially simple carbohydrates like bread, or glucose-fructose (corn syrup) added to “natural” foods as a sweetener, or dextrose (corn sweetener), none a natural occurring compound, all man made focused on making money.
    We have been tampering for so long with our “fuel” that the imbalance we have pushed into our environment is catching us up really fast. Dr. Sears’ books and nutrition advice rings common sense and prudence, it is nothing out of this world, we have modified our feeding habits for so long that not eating a doughnut seems unnatural when before doughnuts or French fries there were fruits and vegetables.
    Returning to our natural eating habits will give our kin a better chance for the future, this if we do not want to see our species fade into the darkness due to natural selection.

  10. What about the view that we were created in perfection, lost that perfection relatively quickly, and have been dealing with death and disease ever since? Fortunately, with advances in science and technology, we are better able to understand – and appropriately respond to – the decay that is happening, which leaves each generation worse off than the one before.

    • Julie,

      Perfection is an absolute term that polarises or epitomises an ideal on something lost, something that we never acquired or never lost, just an ideal, this world is made up of trial and error, successful species live and thrive around the world disregarding our believes due to their ability to adapt to change. Our self conscience fuels our fears, internal, personal, intimate, but nonetheless individual feelings of loneliness, science and technology are our intelligent answer to changing trends, and as such we can not help but wonder if that self consciousness has done nothing more than clouding our survival instinct with fear and uncertainty.
      Returning to basic feeding habits will give those who embrace it a better chance of survival for future generations, not this one, or the next, we will be able to see the outcome only a few thousand years down the road. The key remains on loosing the short sightedness that we, as in personally, will be able to see a dramatic improvement in our lives by taking such and such pill or amino-acid or enzyme or vitamin that will miraculously save our lives and improve its quality.
      Let us not fool ourselves, the way we eat now will influence our children and our children’s children, not us, we will see benefits on the short term, but the true beneficiaries will be our inheritors down the road, long after we are gone, if we truly care about our kin, what better inheritance than truly robust genes.

  11. “You seem to be implying that genes come from the mother” ..another commentor says…

    Barry…epigenetic…is a big word….and confusing. I have always wondered about the mass population effect of birth control pill usage…..as any and all “endocrine” cohort and other clinical research studies……rarely score for years of egg exposure to these drugs….

    Maybe the 4 year olds with DM have 2 or 3 generations of germ cell exposure to BCP’s??
    Thanks for the citation. I will check my 23 and me account to keep track of the gene….

    • You are right the epigenetic is a big word, and more importantly an exceeding complex concept. What it really does is to force us to stand back and wonder at the complexity of gene expression and the environmental factors that do into it. The upside is understanding you have a lot of control over gene expression by your diet and lifestyle.

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