Intermittent Thoughts on Intermittent Fasting - The Switch: Introducing the AMPK vs. mTOR Metabolic Seesaw
|Figure 1: The mTOR - AMPK "cycle" can become a vicious one, as soon as its natural balance becomes disturbed by external, mostly nutritional and/or exercise related factors. Intermittent fasting could help you restore the balance.|
We already know that both fasting and exercise trigger increases in AMPK enzyme expression, which in and out of itself acts as an intracellular sensor that registers elevated AMP/adenosie tri-phospate (ATP) and inorganic phospate(Pi)/phosphocreatine (PCr) ratios - in short, it registers when you are running out of fuel. It is thus obvious that the main function of AMPK within muscle cells is to maintain energy stores at homeostatic levels. In order to achieve that, the 5’-adenosine monophosphate (AMP)-activated protein kinase enzyme upregulates catabolic processes and downregulates anabolic processes. The (entailing) overall effects the phosphorylation, i.e. the activation, of AMPK has on your metabolism are yet more complex than this dichotomous distinction would suggest - its tissue specific effects are illustrated in figure 2:
|Figure 2: Downstream effects the "activation" of AMPK has on liver, muscle, and fat tissue.|
Now, it would be paradigmatically short-sighted to draw the bro-scientific conclusion that you, as a physical culturist, should do everything in your power to avoid the phosphorylation of the 5’-adenosine monophosphate (AMP)-activated protein kinase enzyme to harness the power of permanent mTOR-activation. As mentioned in the last installment, AMPK and mTOR, i.e. the mammalian target or rapamycin, are antagonist - yet not in the sense of a switch with two mutually exclusive positions, but rather like two kids on a seesaw: where one can only go up, when the other is going down.
Proteine kinase seesawing for beginners
|Image 1: Seesawing ain't working if you are trying to do it with someone who does not allow AMPK to come into it's own (img perceptasmile)|
With the constant abundance of readily available energy and, consequently, a low AMP:ATP (~used to usable energy source) ratio, the AMPK-related phosphorylation TSC2 and RAPTOR (cf. figure 5), which in turn would inhibit mTOR activity is absent. Now, what sounds as if it was taken right from a body builders well-spray-tanned dreams, is in fact as unhealthy as it is unnatural. Not only does it block all the beneficial effects of AMPK, i.e.
- increased glucose uptake in liver and muscle,
- increased fatty acid oxidation,
- reduced glucose and fatty acid synthesis, and
AMPK vs. mTOR in energy regulation, health and disease
The seesaw analogy should have made it quite clear that not mTOR or AMPK, but mTOR and AMPK and their interplay constitute the fundamental backbone of an energy sensing and growth regulating system, we have inherited from our earliest, eukaryote ancestors. And with many (if not all) of the major health problems of the Western society being related to a profound disturbance in energy regulation, it is by no means surprising that the chronic (over-)expression of the mTOR pathway (as exemplified by our overweight seesawer from image 1) that is so characteristic of our world of nutritional abundance has recently been implicated in all sorts of...
[...] disease states, where growth is deregulated and homeostasis is compromised, namely cancer, metabolic diseases and ageing (Zoncu. 2010).Assuming that you have read all previous installments of this series, this should make you sit up: Cancer, metabolic disease (obesity, diabetes, hyperlipidemia,...), even aging (cf. figure 3)... in the past Intermittent Thoughts you have not only read about all of these, but you have also seen that intermittent fasting, in the form of either alternate-day-fasting, or Ramadan fasting was able to ameliorate or even partly reverse all these ailments of an obesity-stricken society, which is about to drown in fructose-corn-syrup and partially hydrogenated vegetable oils.
|Figure 3: The contribution of a chronic overactivation of the mTOR pathway on aging |
(based on a review of the literature by Zoncu. 2010)
|Image 2: Do you too have a question related to AMPK, mTOR or Intermittent Fasting, in general? Don't be shy and send it in! Questions, comments and suggestions for future installments of this series can be posted either at the Suppversity Facebook wall, via Twitter or right in the comment-area at the bottom of this page.|
|Figure 4: Merely illustrative sketch of the interplay of mTOR and AMPK as a function of time [in h] with feeding / fasting periods at the indicated time points.|
|Figure 5: Graphical illustration of the way growth factors, substrate availabilty (amino acids) and energy supply / shortage regulate cell growth and metabolism|
Carbing up immediately post workout could help you to make the most of the feeding window
Against that background, even low-carbers may suddenly see some sense in adding a reasonable amount of simple sugar to their post-workout shake, especially if they position their feeding-window right after their training session at the gym (which would then obviously have been performed in the (semi-)fasted state). The fast acting carbohydrate would then not only replete the muscle glycogen stores, they would also allow the amino acids that come with both the post workout shake, as well as the subsequent whole-foods meal(s), and the training and nutritionally induced growth factors to do their anabolic magic by releasing the "catabolic AMPK-break" as fast as possible.
|Image 3: To "carb up" after exercise simple dextrose is probably enough. It does not have to be the expensive Vitargo. And certainly not WaxyMaize, which has a profoundly reduced 4-hour glucose and insulin responses compared to maltodextrine / sucrose (Sands. 2009)|
I would yet assume that you have ingested more than enough information on funky acronyms and modeled signaling pathways to stimulate the neuro-anabolic lEARNing pathway in your brain, so that the intellectual stimulus would ward off any non-beneficial catabolic effects of acute Intermittent Thought deprivation until the next installment will be available - this, I hope, will happen earlier than you may expect ;-)