Molecular biological reasons for switching to a healthier diet!


Two articles just published this week by a Boston-based research team have implicated Western high-fat diets in risk for metastasis of prostate cancer.

The two papers are both by Chen et al. (one is in Nature Genetics; the other is in Nature Communications). However, these are complex papers on the genetics of risk for cancer progression, and many readers may find this commentary on the ScienceDirect web site a little easier to digest. Your sitemaster certainly did!

What Chen et al. are telling us is basically that they have been able to identify specific genetic reasons and biochemical rationales for the hypothesis that men who eat a Western high-fat diet and who get prostate cancer are at potentially greater risk for metastasis because they may have lost both the PTEN tumor suppression gene (which can occurs in up to 70 percent of men with prostate cancer) and the so-called PML or promyelocytic leukemia tumor suppression gene as well. Apparently about 20 percent of tumors in men with metastatic prostate cancer have lost both the PTEN and the PML genes.

According to the commentary on ScienceDirect:

When they compared the two types of tumor — the localized ones lacking only the PTEN gene versus the metastatic tumors lacking both genes — the researchers found that the metastatic tumors produced huge amounts of lipids, or fats. In tumors that lacked both PTEN and PML tumor suppressing genes, the cells’ fat-production machinery was running amok.

They were also able to show that the PML gene was present in the vast majority of men who had only localized prostate cancer.

Then, using a mouse model, the authors showed that their mice were more likely to transition from having indolent, low-risk, localized forms of prostate cancer to high-risk, metastatic forms of prostate cancer if they were fed the mouse equivalent of a Western high-fat diet.

Now your sitemaster would point out that eating a high-fat Western diet certainly can’t be the only reason that men get metastatic prostate cancer! However, it may well be adding to one’s risk, and there are all sorts of other really good reasons why a high-fat Western diet is liable to be a bad idea (starting with cardiovascular disorders and diabetes).

What these two articles by Chen et al. are telling us — yet again — is that the average high-fat Western diet is not one of the greatest ideas when it comes to healthy living over time. That is especially true when it is combined with a lack of regular exercise. So, rather than worry about the detailed explanation about exactly what genes may be involved and the precise biochemical explanations of why (which are certainly going to be fascinating to some researchers in the field of molecular medicine and molecular biology) …

Cut back on the steak and fries.Substitute less fatty products (veggies, nuts, etc.). … And take 30 minutes of serious regular exercise each day! It’s just an all-round good idea!

14 Responses

  1. Thank you. Very interesting research! However from reading the commentary cited above, it seems that what they fed the mice to get them sick was not simply a “high fat diet” but was a “high saturated fat diet”. So it might not be a problem to continue eating a Mediterranean style diet which is not a low fat diet (compared to Ornish for example) but has nuts, avocadoes, olive oil, and fish in abundance, all of which provide unsaturated fat.

    I wasn’t able to read the Nature Genetics article since that is behind a paywall, so I’m wondering if there’s info in there that suggests that high fat of any kind is a problem, or really if the problem is focused on high saturated fat. Any thoughts?

  2. I wonder are high fat foods that aren’t animal based (e.g., avocados, olive oil) also implicated in the same way?

  3. Dear Anonymous and John:

    Apparently I wasn’t specific enough. The research team is clearly talking about saturated fats.

  4. Thanks!

  5. Worth mentioning that several articles mention fatostatin, an obesity drug, as a “precision” therapy that interferes with the impact of PTEN and PML mutations. Trials are likely to see whether this drug will inhibit metastasis.

  6. Dear Rick:

    There isn’t a single clinical trial of anything called “fatostatin” mentioned on the ClinicalTrials.gov web site. I think this may be a case of the research community making assumptions about the clinical development of a drug that may not be worthy of development. Just because something does something in a Petri dish doesn’t mean it has the potential to become a therapeutically valuable agent.

    It appears that fatostatin was identified in at least 2009 or earlier. This would suggest to me that if it actually had any potential as a statin that reduced people’s weight, someone would have tried to develop it by now. We desperately need good weight loss drugs.

  7. Hi guys,

    Here’s a link which gives some info about fatostatin potential in this regard.

    John

  8. Don’t shoot the messenger, Mike … all I am relating is that trials are likely — not that they happened yet. For many who read The New York Times article, it reports:

    “Now the scientists are planning a clinical trial in men with prostate cancer to see if the obesity drug (fatostatin) may be an effective treatment for this cancer. “That’s really important,” Dr. Abate-Shen said. “Aggressive prostate cancer is lethal, and there are no curative drugs right now.”

    Mark you, in this day and age we cannot believe everything we read, especially from such a reputed exponent of “fake news” as the NYT … !!

  9. Dear Rick:

    If I wanted to “shoot the messenger”, I assure you I could do so with a great deal more accuracy. You are missing my point entirely.

    To date, as far as it is possible to tell, fatostatin has only ever been given to mice. There is therefore no data that tells us whether this drug can be given safely to a human. The vast majority of chemicals that get tested as potentially therapeutic agents fail at this step for the simple reason that their toxicity levels make it impossible to use them as drugs in man. “Planning a clinical trial” will only be possible after we know whether fatostatin can be given to humans at all.

  10. The way I read the NYT article, Beth Israel/Dr. Abate-Shen is planning such a trial!

    “Now the scientists are planning a clinical trial in men with prostate cancer to see if the obesity drug (fatostatin) may be an effective treatment for this cancer.” … Seems pretty clear to me, Sitemaster — what am I missing?

  11. Rick:

    We all seem to be missing any data that says this drug can be given safely to anyone.

    Doing a trial in otherwise healthy men with specific genetic characteristics (and a poor diet) as an agent to prevent development of prostate cancer would presumably need these men to be on fatostatin for years.

    To do such a trial we’d better find out first whether this drug can be given to anyone for even a few weeks without significant toxicities. I would sincerely hope that no IRB would approve the sort of trial that you think Dr. Abate-Shen is talking about until we had answered the much more basic safety question. This is a serious medical ethics issue. All statins developed to date have significant risk for potentially serious side effects. My memory is that one had to be taken off the market. These are not necessarily “benign” drugs at all.

  12. Fatostatin is more likely to be trialed as a precision drug for men with PCa that harbor PTEN and PML mutations …. and possibly P53; not as a prophylactic drug to prevent PCa.

    Any diligent IRB will investigate the safety of a drug to be tested for the first time in an in vivo human model. While statins as a class of drugs, do have significant side effects, they are way less toxic than many other drug classes used in the treatment of advanced cancer.

    Bottom line … as reported originally with which you took issue — “trials are planned”. And of course they will have to pass all requirements first.

  13. Dear Rick:

    All I have ever said is that fatostatin has never been used in a human at all. Until that has been done, it doesn’t matter what someone is speculating that it might be able to do. Tens of thousands of drugs that have seemed to do wonderful things in mice and Petri dishes have turned out to be completely useless (or truly dangerous) when given to humans. My only point is that speculation without sound, basic information is not either good science or good medicine. It’s hype.

    For starters, there is no current information that would allow anyone to tell what an appropriate dose of this drug might in any patient with any disorder! And fatostatin is clearly not being “investigated for the treatment of obesity”. No one has published anything about this drug in treatment of obesity since 2009!

  14. LIke I said … I am not the one speculating; I am only relating what the New York Times reported. Maybe you should write them a letter …

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