Fas times at inflammation high

December 2nd, 2009  |  Published in Stumpblog  |  5 Comments

For the biology nerds in the group, here’s some interesting work on how obesity functions as an inflammatory state. The basic premise, as I’ve indicated in previous posts, is that a “critical mass” (if you will) of adipose tissue produces a particular hormonal environment, because fat tissue is hormonally active.

In obesity, write the authors, “excess adipose tissue accumulation is accompanied by local inflammation, characterized by infiltration of inflammatory cells and by elevated production of proinflammatory cytokines, jointly activating inflammatory pathways in adipocytes… [T]he consequent alteration in the composition of secreted products from adipocytes contributes to both local and systemic insulin resistance. Particularly, liver insulin sensitivity can be impaired by obesity-induced alterations in adipokine secretion and by elevation in fat tissue–derived cytokines and fatty acids.” [Translation: more fat equals more inflammation, which creates insulin resistance, particularly in the liver.]

A cellular receptor known as Fas or CD95 is an important player here. Fas, when activated and behaving itself, generates apoptosis — necessary cell death. Normally, this is a good thing. You don’t want diseased or dysfunctional cells hanging around. So, apoptosis ensures that the sick and old of the cellular herd are “sent away to live on a farm”. It’s like nature’s housekeeper.

But sometimes Fas can be a naughty little monkey and “induce non-apoptotic signalling pathways”. It can stimulate inflammation and consequently insulin resistance. “For example, in different cell lines and tissues, Fas activation was shown to induce secretion of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8 (KC), and MCP-1, rendering it a potential key component of the inflammatory response… Our findings point toward an important role of adipocyte Fas expression in the development of obesity-associated fat tissue inflammation and insulin resistance.”

In insulin-resistant mice as well as obese and diabetic patients, Fas expression is increased. F-A-S spells B-A-D. On the other hand, mice genetically altered not to have Fas are protected against this obesity-induced insulin resistance, which includes protection against liver steatosis (fatty liver, which is a less-known yet potentially more damaging element of metabolic syndrome).

This suggests that there may be treatments in future that address the Fas expression. At the very least it offers new understanding of the relationship between obesity, inflammation, and associated consequences.

Link to full study

Responses

  1. Alicia says:

    December 2nd, 2009at 9:09 pm(#)

    Krista, do you have the sense that the average practicing physician understands these relationships?

    I’ve just started learning about chronic inflammation recently, but my own doctor hasn’t hinted that he sees it connected with my obesity. (In fact, I had to push hard to get him to allow a leptin test, because he didn’t have a course of treatment to follow if it came back too high, which it did.) I know it takes a while for medical research to make its way into general practice, but I don’t know how long.

    What are your thoughts?

  2. Mistress Krista says:

    December 3rd, 2009at 7:21 am(#)

    Alicia: I suspect that the average doctor does not. For one thing, doctors are rarely trained to think systemically — they are trained to think symptomatically. Consequently they often conceptualize diseases or symptoms as isolated, discrete events. This has prevented us, for example, to make progress on broader concepts such as “cardiometabolic risk” — in other words, the idea that heart disease and diabetes are manifestations of the same underlying phenomenon. Because, y’know, heart disease is fat and diabetes is sugar, so they can’t possibly have any relationship. They also tend not to grasp patients as emblematic of their environments and genetic histories. I think this is really due to the type of training.

    However, you can help your doctor to do his/her job. For one thing, compiling a very clear written list of your symptoms and signs is extremely useful. Doctors are often frustrated by people coming in with vague complaints and forgetting pieces of relevant information. Getting it all on paper helps them identify connections.

    Second, while this may piss doctors off, bringing clinical studies in to show them can be quite useful (especially if you have more than one). I’ve sent my father to his doc with data on statins and muscle damage, and she was forced to acknowledge that his unusual calf injuries could be related to all the statins she’s prescribing, so they are working together to lower the dosage. Family docs don’t have a lot of time to keep current on the journals, so helping them be aware of new research can also assist them.

    The more you can understand your own situation, the better. Then you can help other people understand you.

  3. Alicia says:

    December 3rd, 2009at 7:26 pm(#)

    Interesting. Thanks for sharing! Considering how patient my doc is with me saying “I read it online” I bet he’d love to see some studies. :)

  4. Sara Anderson says:

    January 8th, 2010at 1:21 pm(#)

    I’ve been diagnosed with a form of MS, so I’ve been researching this kind of thing for the past 2 years(as a pretty darn smart layperson), and I think this theory is about to go from crackpot to mainstream.

    And I want to know who all these terrible doctors are that never think systematically. I lucked out with a particularly good GP, but a lot of trashing of mainstream medicine doesn’t add up with my experiences. Specialists can be that way, most definitely.

    I’m in a quasi-medical field, so doctors tend to assume I can keep up with their thought processes, and it kind of gives me an uncommon advantage in my medical care.

  5. Mistress Krista says:

    January 8th, 2010at 4:34 pm(#)

    Sara: If you have had great doctors, that’s awesome. Ideally that should be all our experience! However, the reality is that many folks have symptom-focused medical care. I’ve experienced it, and so have family and friends. Just like every profession there are good ones, bad ones, lots of mediocre ones, and a handful of great and awful ones.


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