A study of how genetic factors determined diet-induced epigenetic changes

This 2016 California rodent study found:

“HF [high fat] diet leads to persistent alterations of chromatin accessibility that are partially mediated by transcription factors and histone post-translational modifications. These chromatin alterations are furthermore strain specific, indicating a genetic component to the response.

These results suggest that persistent epigenetic modifications induced by HF diet have the potential to impact the long-term risk for metabolic diseases.”

The experimental procedure was that 7-8 week old subjects of two mice strains “were placed on three diet regimens:

  1. control diet for sixteen weeks,
  2. HF diet for sixteen weeks, or
  3. HF diet for an initial eight weeks followed by control diet for eight weeks (diet reversal).”

On diet regimen 3, one of the mouse strains wasn’t able to reverse the epigenetic changes caused by eight weeks of a high-fat diet. The symptoms included:

  • Elevated lipid accumulation and triglyceride levels
  • 15% of chromatin sites were more accessible, with the HNF4α transcription factor implicated
  • 6% of chromatin sites were less accessible due to H3K9 methylation
  • Persistently up-regulated genes were more likely to be in the vicinity of a persistently accessible site
  • A set of persistently up-regulated genes enriched for mitochondrial genes was present only with diet regimen 3 subjects.

A second mouse strain “known to display differences in metabolic dysfunction under HF diet” compared to the first strain didn’t experience the same symptoms on diet regimen 3:

  • Lipid accumulation and triglyceride levels weren’t elevated
  • The majority of diet-induced chromatin remodeling [was] reversible
  • Little overlap with the first strain in the set of genes that changed expression.

The study didn’t suggest any specific human applicability.

http://www.jbc.org/content/early/2016/03/22/jbc.M115.711028.long (pdf) “Persistent chromatin modifications induced by high fat diet”


3 thoughts on “A study of how genetic factors determined diet-induced epigenetic changes

  1. there is more to this in the bigger article this week. good work art


    Dr. Arthur Janov and Agustin Gurza

    It’s hard to fathom what qualifies as front-page news in the Science section of the New York Times these days. On February 23, the newspaper ran a profile of a psychiatrist whose drug treatment approach was trumpeted as groundbreaking because it was “based on science.” Some 2,500 words later, we realize that the treatment is not novel nor revolutionary, and neither is the science it’s based on. In 25 words or less, the story can be boiled down to this: Shrink thinks addiction is genetic; prescribes psychotropic drugs and psychotherapy to help patients kick the habit.

    I’m sorry, but that’s not news. To me, the whole thing sounds completely conventional. The doctor states that medication is necessary to reduce the cravings that drive addiction. He believes that the main target is the craving; so it is okay to use drugs to reduce the craving. One question is never really addressed: where do these cravings come from? That remains a mystery. There is no recognition of a deep inner life, of the early pain and unmet needs that are at the root of addiction and many other disorders. There is no exploration of those root causes, how they become embedded and imprinted as memories, and how they endure for a lifetime, forever fueling those mysterious cravings.

    Yet, understanding the real roots of addiction is precisely where the real science comes in. If you don’t know the cause, how can you prescribe a cure?

    The focus of the doctor’s approach is on inhibiting the desire for drugs, by a mix of meds and a mish-mash of treatment modalities, from cognitive behavioral therapy to short-term counseling. And oh yes, did I mention breathing exercises? They have added that to the mix. Even allowing patients to smoke weed in moderation is part of the plan.

    So here we have a story about drugs used to stop drug addiction. And this is revolutionary? Is there ever going to be a realization of why we need drugs in the first place – a description of inner life and above all, of our early history? Or are we just rearranging chairs on the Titanic? Because down below there really is a catastrophe lurking; the boat is sinking. And what is being treated? Only the behavior we can see in the present, the symptoms on the surface.

    The article in question, entitled “Rehab Rooted in Science,” tells the story of Mark Willenbring, a psychiatrist who runs an outpatient clinic for drug abuse in St. Paul, Minn. The crux of the story is that Willenbring, a former director of the National Institute for Alcohol Abuse and Alcoholism, grew frustrated with traditional rehab centers that based their treatment on abstinence, replacing addiction with discipline. Most such rehab programs, the story states, are based on the outdated 12-step principles of Alcoholics Anonymous, which tells addicts they have some sort of moral defect and must “surrender to a higher power to escape substance abuse.”

    Rehab had created a revolving door for patients who were always in-and-out of treatment, feeding the $35-billion-a-year treatment industry. Like the patient described in the story, a young man who had been addicted to heroin for years, had tried a score of treatments, including faith-based programs and a punishing boot camp for teenagers, then tried to kill himself by downing an overdose of Xanax. When the suicide failed, he overdosed on heroin.

    It was obvious to Willenbring, who had built a career studying and treating drug addiction, that AA’s 80-year-old approach wasn’t working. “One night while walking his dog in a snowstorm,” the Time story states, “Dr. Willenbring wondered why so few of his patients were able to abstain from drugs and alcohol.”

    That’s precisely the right question. Unfortunately, he missed the answer.

    The doctor’s first step is to tell the patient that the addiction is not his fault; it’s not due to his character weakness or moral failings. And so far, so good. I agree that no patient should be blamed for the childhood trauma and pain that leads to this kind of suffering in adulthood. But the good doctor doesn’t try to address those early feelings that are feeding the addictions, as we do in Primal Therapy. In fact, the patient’s feelings aren’t factored into the solution at all.

    Instead, Willenbring tells his patients – with astounding precision – that the problem of addiction is 60 percent genetic. But exactly how does he know? The new science of epigenetics now tells us that life experiences can have a profound impact on our genetic makeup through a chemical process called methylation. In other words, our genetic code is not fixed by inheritance but rather it can be distorted by what happens to us in life, starting in the womb.

    So it’s not enough to say, “Don’t worry, your addiction is genetic.” Real science now compels us to explore treatment that might help us reverse epigenetic damage, as we believe occurs in Primal Therapy through reliving those buried traumatic memories. However, that is not what Dr. Willenbring recommends at Alltyr, the St. Paul clinic he founded in 2012.

    Instead, his treatment strategies rely heavily on medications to treat everything from depression and A.D.H.D. to chronic pain and PTSD. Then there’s the anti-relapse medications.

    “He prescribes medications to reduce alcohol cravings,” the story states, “along with Suboxone to eliminate opioid cravings and block their highs…Dr. Willenbring is adamant that for many, such drugs are crucial for a safe recovery. Long-term use of opioids can halt the brain’s mechanism for producing its own painkilling chemicals, he said; without replacement drugs, many users remain in continuous discomfort.”

    Wait a minute. So he credits one drug for helping patients get off other drugs. Is this a clinic for addiction? Sadly, it touts itself as an improvement on other approaches. So explain to me how and why? It is not enough to use drugs to cure drugs. That is an oxymoron. What is needed is a really new approach, an awareness of a deep inner life, a therapy that addresses the imprint down in the antipodes of the brain where it creates havoc and unrelenting need. It is unrelenting because it results from a memory imprint that is imprinted into the genes of the system and endures perhaps for a lifetime.

    Let me start with one truism. We are addicted to need, not to any substance. And you do not conquer need. Need is essential for fulfillment and development. It cannot be denied or avoided. It is an immovable object. Above all, we must understand how personal evolution gets detoured, which means we must examine epigenetics and methylation. We must understand what lies below addiction and why it exists.

    And what lies beneath addiction – or any neurotic, destructive behavior – is need. That behavior or drug has to block need and the pain it engenders. Are we addicted to sex or are we addicted to the need for touch, for the caresses, hugs and kisses that we missed early in our lives? Those alterations become part of our systems and drive behavior. They have the importuning quality of life and death because they derive from deep and life endangering pain.

    So let’s see what Dr. Willenbring brings to us: suboxone, which has elements of an opioid in it, joined with naloxone which blocks the effects of an opioid. This latter helps undo a bit of repression. It is basically an opioid antagonist. Why that? Because they have also offered a wee bit of the drug they are trying to detox.

    In Primal Therapy, we too see behavior but of a very different sort: the behavior of those who address and relive their history with all of its agony. We don’t have to confine ourselves to what is obvious, taking drugs. We reach the bottom layers of the brain which contain feelings, needs and pain so that we can finally find relief from their terrible control over our lives. By contrast, our good doctor brings relief but no resolution, a big difference. But if you have no way to observe deep into the nervous system then you are confined to the superficial. This is what Primal Therapy offers: a deep look at the changes in the brain, so that we understand the importance of the new neurology: epigenetics and methylation. We can now measure the pain and measure its resolution; that is science at work, no surmise nor guesswork. Neurology has opened up a whole new dimension to us. Let us not neglect it. If we do, it is at the patient’s peril.

    Can we imagine the lifetime effects of never reaching the pain and leaving that deleterious force to do its damage over the decades? No one escapes; no one who has unaddressed pain stays untreated with impunity. Repression always has a price, and it will take its toll. Caveat emptor.

    In the Times story, Dr. Willenbring laments that the drug treatment industry turns a deaf ear to critics and a blind eye to recent scientific research. He complains that rehab centers are set in their way and their proponents refuse to listen to the science that is showing the path to a more effective alternative.

    “When the facts change — and they’ve changed a lot — the minds have not,” Dr. Willenbring said.

    Now he knows how I feel.

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