Sunday, February 12, 2012

Intermittent Thoughts on Insulin Resistance: Fats, Carbs & Lack of Exercise - Where is Our Scapegoat? Plus: Chicken or Egg - Which Came First Obesity or Insulin Resistance?

Image 1: You may think it's ugly because it is not comply with the current beauty ideal, but this small quantity of subcutaneous is probably rather a sign for high insulin sensitivity, than resistance.
In the last installment of this series, I tried to establish a new, a certainly unconventional perspective on a physiological process many people consider the #1 plague of the 21st century: Insulin resistance. As it turned out, the desensitization of our cells to insulin and the subsequently reduced glucose uptake into the cells, can be an advantage. In the course of a marathon, for example, it helps our bodies to maintain a relatively stable blood sugar level and shift from a largely glucose-dependent to a more fat-dependent metabolic state. The existence of this often overlooked beneficial side of insulin resistance does yet bring up the question, why insulin resistance and obesity usually go hand in hand. I mean, if insulin resistance turns you into a fat burning machine, how come that obese people, of which many (but not all!) are in fact profoundly insulin resistant, don't just burn off the superfluous body fat? And how come that the number or normal weight persons with insulin resistance or type II diabetes is steadily increasing?

Obesity and insulin resistance, chicken, egg or just a huge misunderstanding?

To answer these and many related questions we will first have to look at the context in which both develop: The affluent western convenience society,  with its sedentary fast-food munching, coke-guzzling citizens. Yet while I suppose that we (and all experts) the culprit lies somewhere within one of the attributes to "citizens", there are huge differences at least with regard to what different individuals identify as the main culprit.
  1. There are the friends of mathematics, who have no clue of either physics or the physiology of the human body, who will say that the underlying problem lies with the first attribute, i.e. lack of exercise, or more precisely, a positive "energy balance"
  2. The second group of "experts", believe that all the fatty grease from the burgers and french fries would be paving its way from our intestines outwards to our bellies (well, sort of ;-), recommend a healthy low-to-no fat diet as the one size-fits it all solution to insulin resistance and obesity and apparently believe that this will also cure heart disease, prevent cancer and diabetes - you know the whole litany
  3. Thirdly, there are the low-to-no-carbers who believe in the doctrine of Dr. Atkins and thusly hold the firm believe that the third attribute (as well as the buns of the burgers and the fries, themselves, obviously), i.e. the overconsumption of carbohydrates in general and high fructose corn syrup in particular is to blame for the current misery.
I guess, if we just voted on which is the "right" hypothesis, the results would not be very balanced. This may thusly be lustig (which means "funny" in German ;-), but would not contribute any deeper insights into the etiology of either or both of the aforementioned phenomena, which were - just in case your brain is either suffering from a lack of glucose (this would indicate you tend towards position 3) or already sugar coted, like the guaranteed fat-free lolly in mouth - obesity and insulin resistance. I would thusly suggest that we put aside our idiological biases, of which I just want to casually mention that they are largely determined by our personal success / failure with exercise and or low fat or low carb diets, for a few minutes and take another look through our "our body knows best"-glasses.

Hey body, are you waiting for the great famine?

Image 2: These kids are obviously
preparing for the big famine.
When we look through these glasses at the (morbidly) obese diabetic end-products of a painfully slow process, which - for most people - stretches over the better third of their lives, the often touted "only the fattest survive(d) the famine" hypothesis would be the only  reasonable explanation for all the mess. That is actually quite nice, because we would thusly be able to blame our "thrifty" genes, lean back and wait for the famine to come, when all those anorexic cover models will eventually parish while we would take advantage of the glucose sparing effects the insulin resistant state we are in has to offer and live off the truckloads of body fat we have accumulated over the years happily ever after.

Now, even we assume that the aforementioned cover models were not only anorexic, but also stupid enough not to slaughter and cannibalize us before they starve (I guess the low fat fraction and the vegans among them would chose the latter ;-), the fattest among us will probably still be the first, not the last to die.

Did you really tell me not to eat that pie, body? Am I just a glutenous slob?

While it may be correct that we are evolutionary designed to store energy in the form of body fat (not calories, cf. "1lbs of fat does not equal 3500kcal"), our "our body knows best"-glasses allow us to see that our fat tissue is well aware of its own limitations and uses a broad range of adipokines, most prominently leptin, to inform the brain and the other organs about its current filling level. Now, the infamous "free will", a purported privilege of the glorious human race, would obviously allow us to ignore the clamor that is coming from our hips, bellies and buttocks, and at least in the "just a little chubby"-stage of the process this may in fact be part of the reason - "Ah, granny, I am full, but that delicious last piece cake will still fit in!"

After years on granny's delicious cakes, and another 50lbs of pure fat on our hips and amidst our organs, our "free will" is yet going to be the least of our problems. Now that our adipose tissue is crying at the same decibel level as the engines of one of those Airbus A380 mega jumbos and our brains (I am talking about their "unconscious" part here) are long deaf, it is almost too late to make better use of our "free will" and finally refuse yet another piece of one of granny's oh-so-delicious pies.

I am fat! How can I be hungry and still gain, not lose weight?

Image 3: There comes a time, when it is not only about making the "wrong" food choices. A time, when neither the apple nor granny's pie will satisfy your hunger, and your cells will be starving within an nutritious cocktail of partially oxidized fatty acids and sticky glucose molecules... yet still, or I should say, exactly for that reason simply "cutting calories" won't solve the problem.
As paradoxical as it may sound, when the number of pies we have stored all over our bodies exceeds a certain limit, our ability to assess and whats more important, to use those valuable energy stores to an extend which will fool the regulatory systems of our bodies to believe that we are starving. And when we look through our glasses, we will see that - at least on a cellular level - this is in fact the case: With the mitochondria of our cells blazing up in flames and the malfunctioning glucose pumps, many of which do not even reach into the blood stream anymore (I guess you understand the reference to non-translocated GLUT-4 transporters ;-), only minuscule amounts of the exorbitant amounts of glucose, which have already begun to clutter the cell surfaces, are finding their way into the cell. And the little additional energy the malfunctioning mitochondria are deriving from the fatty acids which are by now leaking uncontrollably from the porous fat cells, is neither enough to live, nor so little that they would die...

If you are interested in the prequel of this story, which - as it has become increasingly fashionable ever since the release of the "first" three part of the Star Wars saga - will reveal why and how many of us betray the force... ah,  pardon the regulatory mechanisms of our bodies, you will have to wait for the next installment of this series. So make sure you stay tuned during the 7-days science break ;-)