I want to continue posting about AMPK as I learn more. While all my informative posts may be useful and interesting to you readers out there, I am really doing this as a way to organize this information as it’s entering my head. Ha. Which is why it comes across as more like notes taking than trying to present a professional presentation. Writing lets me piece together information puzzles and actually benefits me by slowing me down. All the thoughts in my head can fly around so fast, something needs to step in an slow the them down. So, here’s some more about AMPK.

I found this paper “AMPK as a mediator of hormonal signaling”, and it looked like I could learn a few things from it. So, I figured I’d put all my ‘note-taking’ in this blog post.

AMPK is now known to be an integral part of energy homeostasis on both the cellular and whole-body level. It is known to inactivate two major regulatory enzymes for fatty acid and cholesterol synthesis, and more recently AMPK’s role in carbohydrate and protein has been described. (Self note: must find more about this)

AMPK and Appetite:
AMPK is expressed in the brain mostly in the hypothalamus and hindbrain areas, which are areas involved with food intake and neuroendocrine function. Fasting results in increased hypothalamic AMPK while the re-feeding period results in decreased AMPK expression. This correlates to an increased appetite with increased hypothalamic AMPK.  The reverse is also true.

AMPK and Peripheral Tissues:
AMPK is also expressed in peripheral tissues such as skeletal muscle tissue, the liver, fat, and myocardium. When AMPK is activated, catabolic processes that produce ATP are “switched-on”, so AMPK plays a role in regulating the AMP:ATP ratio in the body.

Note here that activated AMPK results in ATP producing activities. The mTOR pathway is thought to be a cellular “sensor” of ATP levels, and when intracellular ATP levels drop, the end result leads to mTOR inhibition. The following paper I link to below suggests that mTOR may not directly sense the intracellular ATP, but rather AMPK’s sensing of the intracellular AMP:ATP ratio could signal to p70S6 kinase. This enzyme is in a signaling pathway that is includes mTOR.

The paper “A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway” from 2003, discusses the (possible) link between AMPK and the mTOR pathway.  However, they do mention that the mechanism behind the AMPK-mTOR relationship is currently not known – so I must dig elsewhere to learn if this mechanism is now know. Grrr.
/end note

So, continuing with the original paper:

Interestingly, hypothalamic AMPK is also linked to the regulation of peripheral metabolism, and likely plays an integral role in coordination the interaction between central and peripheral energy metabolism. Several metabolic hormones are affected by or affect AMPK activity. These include: Leptin, Adiponectin, Resistin, Ghrelin and cannabinoids, Insulin, Glucagon-like peptide-1, and glucocorticoids.

Here we get into complicated stuff. Since AMPK activity in relation to these hormones is affected in four major regions: hypothalamus, fat, liver, and heart, several hormones and pathways come into play. Currently, I am primarily concerned with induced hypothalamic AMPK activation, so I am going skip over the details of each hormone in this post. If you want to see the details for each of the above listed hormones, please check out the link to the paper.

Exercise and AMPK:
AMPK activity increases in the skeletal muscle following exercise in response to the change in the AMP:ATP ratio. Exercise also affects AMPK in the liver and fat,  but the details are not elucidated in this paper.

Because of AMPK’s relationship to metabolic hormones and energy stasis, it has become a target for those with metabolic abnormalities. (think obese, diabetic, metabolic syndrome)

One drug of recent interest is Metformin
Metaformin is currently used as a diabetic drug, and is known to stimulate AMPK in the liver and muscle, but it also inhibits AMPK in the hypothalamus. As a consequence, metformin has an appetite suppression effect.

Another related drug is Rosiglitazone
 Rosiglitazone is another anti-diabetic drug that is used to reverse insulin resistance and improve glucose tolerance. One of the ways this drug is thought to improve insulin sensitivity is through AMPK activation. Tests show increased AMPK activity in skeletal muscle tissues.

What I want to know is what happens when you activate AMPK in the hypothalamus (besides the appetite increase of course)?  It would appear the mTOR pathway could be inhibited as a result, which could be good for a CR person. And, as long at the increased appetite was not acted on, maybe the overall results would be favorable?

Oh my, will I even answer more questions than I ask? Sigh.  Me thinks it’s time to go back to PubMed to see if I can dig up more info…..