Obsessed with Obesity?: Research Science Exposes Another Reason to Get Your Weight Under Control

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New research indicates that fat cells make chemotherapy drugs less effective. PLUS: We begin a new series about dealing with obesity: Tips Against Tipping the Scale

Obsessed with Obesity?: Research Science Exposes Another Reason to Get Your Weight Under Control

Regular readers of this blog might think we’re obsessed about obesity. The particularly sensitive might think we’re fat-shamers. Not so. We’re with you; we're just reporting the news.

We know you’ve heard that defense before, but really, of late every story we find (not, please note, seek) adds—you should pardon the expression—a layer to what we know about the negative effects of obesity. There just may be reasons doctors and researchers are alarmed by what they deem an obesity “epidemic.”

The latest is that fat cells may also interfere with effectiveness of chemotherapy drugs.

The research

As reported on the National Institutes of Health’s National Institute of Cancer website on December 4, researchers have demonstrated “that fat cells can absorb two commonly used chemotherapy drugs and break them down chemically into less toxic forms, potentially reducing the drugs’ effectiveness.”

The drugs are daunorubicin and doxorubicin.

Previous studies, the NCA staff writers point out, have not shown notable differences in the way the body tolerates chemotherapy drugs between obese and normal-weight people. But those studies have limited their inquiries to drug levels in the blood.

By contrast, the new research indicates that fat cells remove chemotherapy drugs from the “immediate tumor environment.” Steven Mittleman, M.D., Ph.D., a pediatric endocrinologist at UCLA’s Mattel Children’s Hospital and the lead researcher in the study, claims that the study provides “the first evidence, to my knowledge, of fat cells metabolizing and inactivating any therapeutic drug.” [Emphasis his.]

Others see the study’s results as further explanation of the fact that obesity seems to result in poorer results from some chemotherapy treatments.  Nathan Berger, M.D., of Case Western Reserve University in the U.S., is quoted as saying, “This is important new work that shed new light on a mechanism by which obesity and fat cells may cause a worse prognosis for [some] cancers.”

While obesity is associated with “poorer outcomes” in the treatment of breast, ovarian, colon, and prostate cancer, the impetus for the new study was outcomes in the treatment of leukemia. Mittelman says, “This work all started with the observation that children who are obese when they’re diagnosed with acute lymphoblastic leukemia (ALL) have about a 50% higher relapse rate than non-obese children.” 

The ‘tumor environment’

A stand-out term in the new research is “tumor environment,” or in some cases “tumor microenvironment.” That’s where the fat cells seem to do a lot of their dirty work on the chemotherapy drugs. So where is it? In short, is the area immediately around tumor cells.

Previous studies spearheaded by Mittelman found that fat cells reduced the effectiveness of the drug duanorubicin in treating leukemia. What led to the new study’s focus on fat cells was the realization that, in Mittelman’s words, “Many cancers occur in an area [of the body] where there are a lot of fat cells. The bone marrow, where leukemia likes to live, has a lot of fat cells in it. The colon has a lot of visceral fat around it, and breast cancer is surrounded by fatty tissue in the breast.”

Experiments showed that fat cells were able to absorb and “de-activate” the chemical duanorubin and doxorubicin, in the latter drug to a lesser degree than in the former.

In the easy-to-understand lay language of the NCI story: “Finally, the team found evidence that human fat cells produce high levels of several enzymes capable of breaking down anthracyclines like daunorubicin and doxorubicin, which are used in treatment regimens for a wide range of cancers. And they detected some of these enzymes in fat cells from bone marrow of children being treated for ALL.”

The implications for future research and treatment protocols

The latest study found that fat cells reduced the “concentration” of the drugs in the microenvironments. Accordingly, Mittelman and his team proposed additional studies to develop a method “to measure the concentration of drugs in the tumor microenvironment in a living person or mouse so that they can assess the effects of nearby fat cells.

“Then we can test strategies to overcome the effects of fat cells [on the drugs]”…. “We need to know the best way to deliver chemotherapy to obese children, or obese patients in general.” Potential ways of doing include:

  • Giving the drugs more often and/or at higher doses
  • Designing new drugs that are resistant to fat-cell enzymes
  • Developing treatments to block those enzymes

Mittelman also commented, “It’s certainly possible that some other known or soon-to-be-discovered chemotherapies could be taken up or even broken down by fat cells.”

Dealing with obesity

While researchers are dealing with the negative effects of fat cells in studies, their “patients” are dealing with them—or not—outside the laboratory. What’s increasingly clear is that of the identifiable self-propelled causes of diminished health, e.g., over-indulgence in drugs and alcohol, obesity is the most pervasive.

As we’ve written often, the keys to prevention or reversal of obesity are known: proper diet and regular exercise. So in addition to noting that with dulling repetition, we are going to conclude each post in which obesity figures, so to speak, prominently, with a Tip Against Tipping the Scale. They’re things people with a tendency to overeat can take up regardless of the food plan they or their doctors have them on. Things that are doable.

Tip Against Tipping the Scales No. 1: Go to Bed Earlier

No, were not suggesting going to bed right after dinner. That’s a bad idea for more reasons than would fit here.

What we are saying is that most people who have problems controlling their eating have their biggest problems after dinner. The distractions of the day—activities that distract from the desire to eat as a substitute activity—past, the desire to “relax” after dinner sets the stage for boredom-reducing “fun” activities like eating, sweet and salty snacks in particular.

So: do something to indicate to yourself that you’ve finished dinner, let dinner settle and digest, and then turn in. If you’re staying up for the late-night shows, or revving up for some television binge-watching, you’re going to get hungry the farther you go beyond dinner. This is how hunger works.

Don’t fight it. It has the advantage. Go to bed and prepare to sleep before you get hungry again. You’ll sleep better, and it’s far easier to eat the way you really want to in the clear light of morning.



https://www.ncbi.nlm.nih.gov/pubmed/29117945 (study abstract)

http://mcr.aacrjournals.org/content/15/12/1704.long (study full text)

Studies of ALL and child-leukemia recovery rates:




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