34 replies to this topic

[Shepard]

http://endo.endojour...2006-1237v1.pdf

[proteomist]

http://endo.endojour...2006-1237v1.pdf

Excellent, thank you. Exactly the kind of thing I was looking for. For the benefit of those too busy or lazy to click, here's the abstract:

ABSTRACT
The oral antidiabetic agent metformin acts at least partially via an activation of AMPK in liver
and muscle cells. It has recently appeared that hypothalamic AMPK is a key regulator of
feeding in mammals. Since metformin also exhibits anorectic effects in animal models as well
as in humans, we hypothesized that AMPK may be a target of metformin in hypothalamic
neurons. Here we show that in primary cultures of rat hypothalamic neurons, low glucose
levels stimulate the phosphorylation of AMPK, thus increasing NPY gene expression. The
addition of metformin in low glucose conditions was found to block AMPK phosphorylation.
Consistently, the stimulation of NPY observed in low glucose conditions was also inhibited
by the drug. POMC gene expression measured in parallel was inhibited under low glucose
conditions, but in contrast to NPY, it was not dependent upon AMPK and not affected by
metformin. Taken together, our data demonstrate that metformin can inhibit AMPK activity in
hypothalamic neurons, thus modulating the expression of the orexigenic peptide NPY. These
results provide for the first time a potential mechanism of action for the anorectic effects of
metformin, a widely used drug that could represent a valuable adjunct to novel therapies
aimed at modulating central feeding pathways.

[Brainbox]

Could it make sense that people at the lower end of BMI experience increase of appetite while at the higher end appetite is decreased? (As stated by anecdotal reports in the 500mg thread?)

Í also experience increase of appetite. I'm at the lower end of BMI. An anecdotal anecdote, I know. I do not have the knowledge nor insight to investigate this as far as the knowledge is present at all, but could it be dependant on other metabolic pathways that are a dependant on weight, BMI or whatever?

[zoolander]

ok. Lets keep this discussion on topic and about the effects of resveratrol on AMPK. Discussing other compounds that have a similar action but may differ slightly is confusing some people IMO.

[Shepard]

This was a pretty fun paper:

Nutrition. 2008 Sep;24(9):786-90.
Role of hypothalamic AMP-kinase in food intake regulation.
Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S.

Division of Endocrinology and Metabolism, National Institute for Physiological Sciences, Aichi, Japan.

Adenosine monophosphate-activated protein kinase (AMPK) functions as a cellular fuel gauge that regulates metabolic pathways in nutrient metabolism. Recent studies have strongly implicated that AMPK in the hypothalamus regulates energy metabolism by integrating inputs from multiple hormones, peptides, neurotransmitters, and nutrients. Leptin is an adipocyte hormone that regulates food intake and energy expenditure in peripheral tissues. Leptin inhibits AMPK activity in the arcuate and paraventricular hypothalamus, and its inhibition is necessary for the anorexic effect of leptin. Alteration of hypothalamic AMPK activity is sufficient to change food intake and body weight. Furthermore, fasting/refeeding, glucose, and melanocortin receptor alter AMPK activity in the hypothalamus. Adiponectin has also been shown to increase food intake by activating AMPK in the arcuate hypothalamus. Recent data have shown that acetyl-coenzyme A carboxylase/malonyl-coenzyme A/carnitine palmitoyltransferase-1/fatty acid oxidation and mammalian target of rapamycin signalings are putative downstream pathways for food intake regulation in response to hypothalamic AMPK. Thus, these results suggest that food intake and nutrient metabolism are coordinately regulated by the common signaling pathway of AMPK in the hypothalamus.

PMID: 18725075