It’s only 2:30am, so with several hours to go, I am trying to find and fit together more AMPK puzzle pieces. I’m trying to figure out the consequences of increasing AMPK in the hypothalamus besides just an increase in hunger. Since diabetic researchers are interested in learning about AMPK activation in skeletal muscle and the liver, I am having a hard time finding research that meets my searching criteria. Hrumph.


How does hypothalamic AMPK activation affect skeletal muscle activation? This is one more pointed question that I am seeking to answer.

First Paper:::

The paper, “AMP-activated protein kinase in the brain.” looks as though it contains some valuable information, but alas, I only have access to the abstract. Here is the abstract for drooling purposes:
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Since its discovery as an important regulator of fuel utilization in the periphery, AMP-activated protein kinase (AMPK) has become a contender for many important cell-intrinsic and organismal roles regarding energy balance in the central nervous system. The challenge will be to delineate the mechanisms by which neuronal AMPK can respond to cellular energy requirements as well as whole body energy demands. Thus, under physiological conditions in the brain, hypothalamic AMPK responds to changes in energy balance/food intake, whereas under pathological conditions, AMPK responds globally in the brain to energy challenge. Modulation of fatty acid metabolism affects energy balance in a context-specific manner and may provide an insight into other mechanisms for selective activation or inhibition of AMPK activity for therapeutic applications.
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This paper seems very promising, but I don’t feel like paying $32. If I can’t find anything in other papers, I may try to contact the author and ask for a copy.

Next Paper::::

I was able to glean a few possibly interesting bits from the paper, “Central exercise action increases the AMPK and mTOR response to leptin.“. However, the context of this paper is not exactly what I am looking for, so I have to be aware of context. Here are some bits I picked out that may come in handy to know::

Note on leptin and AMPK:
*Increasing evidence shows that leptin and IL-6 activates AMPK in the peripheral tissues, such as skeletal muscle and adipose tissue, increasing fatty acid oxidation and glucose uptake in these tissues, however, leptin has an opposing effect in hypothalamic tissue, reducing neuronal AMPK activity.

Note on Interleukin-6 and AMPK, mTOR:
*[W]e detected changes in the hypothalamic AMPK activity in rats after i.c.v. infusion of IL-6; we show that, IL-6 markedly decreased phospho-AMPK abundance (an index of activity) in the hypothalamus….IL-6 increased mTOR activity; moreover inhibition of central mTOR reversed the anorectic effect of IL-6.

Note on Exercise and AMPK:
*[E]xercise, per se, does not alter AMPK activity in the hypothalamus…In conclusion, exercise improved the AMPK and mTOR responses to leptin administration and contributed to appetite-suppressive actions. This increased dynamic responsiveness of the AMPK/mTOR pathway to leptin could provide information regarding the molecular mechanism underlying the biological sensitivity to leptin in exercise. Furthermore, these findings provide support to the hypothesis that AMPK and mTOR interact in the hypothalamus to control feeding in exercised rats, in an IL-6-dependent manner.

So, I learned about some interesting relationships with this paper, but they are really only tangentially related to what I am seeking. However, these findings may come in handy to know. On to another paper.

Paper Three:::

This paper was a “mind=blown” situation for me, but not exactly what I was looking for; however, since I am on a low sugar diet I find these results worthy of mentioning here. Abstract only, though. Boooo. “Effect of glucose and fructose on food intake via malonyl-CoA signaling in the brain.” From this abstract I would like to point out this::::

“Unlike glucose, however, centrally metabolized fructose increases food intake. This paradox results because fructose bypasses the rate-limiting step of glycolysis and uses a rapid ATP-requiring reaction that abruptly depletes ATP and provokes a compensatory rise in AMP. Thus, fructose has the opposite effect of glucose on the AMPK/malonyl-CoA signaling system and thereby, feeding behavior.“

So, many of you readers probably are aware that fructose doesn’t have the same “stop eating” signaling that glucose does. This paper brings AMPK into play as part of that mechanism. Interesting.

Well, it’s now 4:30am and I am getting too fuzzed to keep up the paper search, so I’ll continue my search tomorrow night. Toodles.