Obesity: Insulin trumps Genetics

I have said it before and I will say it again. Genetics isn’t Destiny. Even when it comes to obesity.

And if you don’t believe me:

Purdue University scientists have uncovered evidence that genetically identical cells store widely differing amounts of fat, depending on subtle variations in how the cells process insulin.

They said identifying the precise mechanism responsible for fat storage in cells could lead to methods for controlling obesity.

Although other studies have suggested certain “fat genes” might be associated with excessive fat storage in cells, the Purdue researchers confirmed such genes are expressed, or activated, in all of the cells. Yet those cells varied drastically — from nearly zero in some cases to pervasive in others — in how much fat they stored.

Their findings indicate that the faster a cell processes insulin, the more fat it stores.

It’s the insulin…it’s the insulin…it’s the insulin.

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14 thoughts on “Obesity: Insulin trumps Genetics

  1. Hi, thanks for posting this. This is very interesting but it also raises the obvious question of what factors influence the rate at which each cell processes insulin?

    Isn’t that rate likely to be at least partly influenced by the expression of other genes? If so, this isn’t evidence that “insulin trumps genetics,” it is evidence regarding which genes are most important, and which processes need to be better understood.

    Is there any evidence that the rate at which cells process insulin is related to the amount of insulin available to the cell? In which direction and under what conditions?

  2. I think the whole fat gene thing is hogwash. Suddenly 65% of the population has a fat gene? But, that being said, our constant sugar spikes do make fat cells fatter. That’s why you want to stay away from a diet high in sugars – which means most packaged food.

    Is it any coincidence that everyone has developed this fat gene since packaged food became popular?

    Your body reacts the same way to artificial sweeteners too.

    Eat real food.

  3. Hi Todd,

    This is what I take from this research:

    We have no control over the genetic hand we have been dealt (ignoring any bleeding edge science..stem cells, etc)
    Insulin is required for fat to be deposited
    The typical Western diet eaten by most of us is essentially designed to induce the non-stop secretion of high levels of insulin
    If we control insulin, we control the expression of the “fat” genes

    While I love the pure scientific research being done into obesity (and the genetic component of obesity), until we get closer to some sort of genetic treatment, those of us that wallow in the trenches of real world weight loss have no choice but to work with what we do know…right now.

    I also realize that insulin control is a sledgehammer approach when compared to the potential solutions being investigated. As our knowledge of obesity grows, it’s likely that science will come up with a more elegant solution to the problem.

    But, for now, I keep seeing more and more research linking insulin to obesity. I also see more and more people losing weight when they control their insulin by replacing high glycemic load foods with low glycemic load foods.

    Thanks for the comment – I appreciate the debate

  4. Thanks for the responses. There is some confusion here I think between two different issues. One of the fascinating question of the specific mechanisms by which we become obese, and what we can do about them. The other is the anachronism of “nature” and “nurture,” and the longstanding popular myth that having a particular allele neccessarily dooms you to a particular long term trait.

    Personally, I am very interested in knowing the mechanisms behind obesity, but have almost no interest in the philosophy of nature and nurture.

    Remember that the time and manner in which a particular gene is expressed is determined by what is going on around it. Your life does not change which alleles you have, but it does change how and when they are expressed. Things like exercise and diet and drugs and so on do not change your genes, but they do change your behavior and body in part by changing the expression of those genes.

    The question of whether there are specific “obesity genes” in some sense (there pretty much have to be, since we are constructed by our genes!) is not at issue. The question at issue is which genes are doing what, how we can influence their activity, and what other non-genetic mechanisms are important to obesity.

    Sorry if I sound like I’m lecturing or stating the obvious, I’m just trying to clear up the misunderstanding here. I wasn’t debating with anyone, I was trying to point out that identifying the role of a gene in a biological process doesn’t automatically mean that you are doomed to some long term fate.

    Also, the rate of insulin processing in a cell and the amount of insulin available to that cell due to are two different questions and I honestly don’t know their relationship and was asking that question.

    Thanks!

    kind regards,

    Todd

  5. Todd,

    Your attitude about this subject is refreshing. Most of what I read about obesity is loaded with emotion. That is why I like to discuss the “pure” scientific research into obesity.

    I really enjoyed your statement – “The question at issue is which genes are doing what, how we can influence their activity, and what other non-genetic mechanisms are important to obesity”.

    However, this type of research can be frustrating because even if a study shows some very promising results, any application is probably years away. Also, quite often the research creates more questions than it solves. great for science, bad for practical application.

    This is the problem we have with your questions about the rate of insulin processing and the amount of insulin available to fat cells.

    The discovery that genetically identical cells store widely differing amounts of fat depending on subtle variations in how cells process insulin doesn’t give us a treatment. All it does is indicate that the faster a cell processes insulin, the more fat it stores.

    According to researcher Ji-Xin Cheng – “Insights from our study also will be important for understanding the precise roles of insulin in obesity or Type II diabetes, and to the design of effective intervention strategies,”

    This work supports an emerging viewpoint that not all biological information in cells is encoded in the genetic blueprint,” said Thuc T. Le, a National Institutes of Health postdoctoral fellow at Purdue who is working with Cheng. “We found that the variability in fat storage is dependent on how 3T3-L1 cells process insulin.”

    “This varied capability to store fat among genetically identical cells is a well-observed but poorly understood phenomenon,” Cheng said

    So, where does that leave us?

    With a new set of scientific questions and the practical conclusion that the expression of “fat” genes is strongly affected by the presence of insulin.

    Nothing definitive, but it’s another piece of evidence I can use to convince my clients/readers to believe me when I cut the Wonder bread out of their diet.

  6. Thanks, DR. Science is to me really about finding regularities in nature. It does a good job at that. Still, most of life is uncertain, chaotic, and heavily randomized in various ways, so I think we sometimes expect science to solve individual problems that are more a matter of learning to solve problems individually under conditions of uncertainty.

    Especially, I think people tend to expect too much from “the latest study.” That’s the way a field makes progress, by replicating and integrating and learning from new observations, but it doesn’t neccessarily have application to individuals immediately, and may not apply directly to individuals at all. The reason why scientific discoveries are cool is that they aren’t obvious, because the generalizations are hidden by the messiness of real interactions. Finding the underlying secret rule among the mess is almost like a magic trick much of the time. But life is as much about the mess as it is about the hidden rules.

    Some experts have proven themselves better than others at showing how the secret rules apply in messy real life.

    For example, on obesity and practical suggestions about it, I particularly like health researcher Barbara Rolls’ books. I learned a lot of practical value from her discussions of the research behind satiety and her applications.

  7. This is a little confusing to me. Would you mind sending me the reference? Is it referring specifically to adipose cells? Which one’s? In humans?

    Usually when we talk about insulin sensitivity we are referring to muscle cells.

    I agree with you 100% that diet/insulin are much more important in fat storage than genetics. I am just not sure exactly what this study is saying.

  8. Scroll down to the bottom of the post – under references is the abstract of the journal article and I just added a pdf of the full study – read the full study at your own risk

  9. The original article helps a lot, actually.

    As I understand it, the authors are most concerned with drug intervention at the level of differentiating cells.

    Toward Darya’s question, they seem to be addressing the problem that different cells early in their differentiation respond differently to the same intervention.

    It is relatively straightforward to use sequencing techniques to study differences due to genetic mutations, but the authors say we lack information available on non-genetic targets.

    So they are investigating a novel measurement technique which takes multiple simultaneous measures from the same cell.

    So far they are finding that differences in cell response in manufacturing fats are dependent on:

    ” the cascade responses of an insulin signaling pathway which includes insulin sensitivity, kinase activity, glucose import, expression of an insulin degradation enzyme, and insulin degradation rate.”

    Toward my question of what specific factors they are studying:

    “Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells. Single-cell profiling reveals the kinetics of an insulin signaling cascade as the origin of phenotypic variability in drug-inducible adipogenesis.”

    So it doesn’t seem to me that they really care very much at all about “insulin trumping genetics,” not are they drawing any conclusions about the influence of heredity at all.

    They care about the specific local mechanisms that cause differentiating cells to build fat differently, and they specifically want to study the cascades related to insulin in more detail using their multiple-measurement technique because it is a relatively unexplored technique, because those are the most promising mechanisms so far, and because differences due to mutation can already be studied by sequencing.

    Is that a fair reading? They certainly do talk quite a bit about cascades for processing insulin, but they don’t really address heredity or diet at all, they care mostly about targets for drug intervention and the usefulness of their new measurement technique, so the article has that focus.

    It’s an interesting technical article, but personally I don’t think I’d title it “insulin trumps genetics” unless I find that I’m missing something. I’m not a biochemist by any means.

  10. Todd,

    I think you broke down the research very well. And I agree with you that the research is focused on drug intervention as opposed to dietary intervention.
    And that makes sense. Ultimately, it will be drug companies that are going to pay for this research.

    That doesn’t mean that other scientists (and lay people) can’t apply this research to other areas of obesity research.

    And I do think that this research lends itself quite well to a nutrition based approach to obesity control.

    The conclusion that “Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells” leads me to believe that reversing an internal environment of increased and prolonged insulin stimulation would help to reverse the accumulation of lipids in those cells.

    With that being said, I am still very excited to see where this research leads.

  11. But isn’t it unfair to blame insulin? Maybe it’s simply semantics but isn’t the production of insulin a natural response to the diet, not the problem. It is simply doing what it is designed to do which is to regulate blood sugar. And honestly back in the day when we couldn’t just open the refrig and grab something to eat…insulin and it’s ability to get energy into the cell for further use is what kept us alive. Just focusing on insulin or glycemic index doesn’t take into account all the factors at play.

    I totally agree that we should be focusing on low-glycemic foods which equates to non-processed foods. But most whole grain products have low glycemic indexes, and I am not talking about “whole wheat bread”. Eating smaller portions and exercise also affects the amount of insulin produced and certain foods are known to improve insulin sensitivity.

    High protein diets don’t stimulate insulin production but they do put excessive loads on the kidneys. High fat diets don’t necessarily increase insulin but those fats are eventually converted into glucose and then eventually stored as fat via insulin.

    I am not disagreeing that overly processed and sugary foods aren’t a big part of the obesity problem and they are everywhere these days…but I am not sure eating scrapple and bacon every morning is the solution. In that sense don’t you worry that focusing on insulin can be misleading and confusing to the masses? It’s kind of like shooting the messenger.

    In the end…if a diet works, great. I think research does support that losing the weight regardless of how you lose it is the key, and if low carbs works for you, fine. I guess I am thinking more about the long term implications of labeling carbs/whole grains bad (just like we once labeled all fats bad) and giving any non-insulin stimulating food the A-okay…bacon would fall under that category…so would scrapple, hot dogs, the list goes on.

    I also wonder about the effectiveness of the message. The nutrition professionals for years have been warning people against sugar and processed foods, yet people are eating more sugar and processed foods than ever before. Sugar and processed foods are the high-glycemic foods. For years, health professionals have been telling people to eat smaller meals which helps to stabilize insulin levels. They have been recommending daily exercise that improves insulin sensitivity and helps to regulate blood sugar levels and burn excess calories…but people aren’t doing it …at least not for the long haul. It almost seems like repacking the same old message hoping this time people will like it and take it home.

    All that rambling aside, intersting research. It’s amazing how much we still don’t know 🙂

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