INT71752

Context Info Confidence 0.39 First Reported 1997 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 17 Total Number 17 Disease Relevance 2.81 Pain Relevance 0.30

nucleoplasm (Prkaa2) nucleus (Prkaa2) protein binding, bridging (Prkaa2) protein complex (Prkaa2) response to stress (Prkaa2) cytoplasm (Prkaa2)

Anatomy Link Frequency hypothalamus 4 skeletal muscle 1 Prkaa2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Intracerebroventricular 75 89.60 anesthesia 31 82.32 agonist 15 60.04 cytokine 16 54.88 Kinase C 1 14.52 imagery 2 5.00 qutenza 1 5.00

Disease Link Frequency Relevance Heat Obesity 585 98.50 Appetite Loss 210 94.52 Aging 15 88.24 Targeted Disruption 1 41.96 Body Weight 60 37.88 Stress 22 16.40 Parkinson's Disease 2 5.00 Immunization 1 5.00 Diabetes Mellitus 1 5.00 Hypoxia 1 5.00

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Event

Anatomy

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Conversely, inhibition of AMPK in the hypothalamus reduces food intake.

Negative_regulation (inhibition) of AMPK in hypothalamus

1) Confidence 0.39 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.06 Pain Relevance 0

-LA results in a greater inhibition of AMPK activity, compared to control animals.

Negative_regulation (inhibition) of AMPK

2) Confidence 0.39 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.16 Pain Relevance 0

In contrast, the pharmacological inhibition of AMPK by ?

Negative_regulation (inhibition) of AMPK

3) Confidence 0.34 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.17 Pain Relevance 0

Both AMPK and ACC phosphorylation levels, reduced by exercise, were reversed by anti–IL-6 antibody (Figure 6c and d).

Negative_regulation (reduced) of AMPK

4) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.32 Pain Relevance 0

Both AMPK and ACC phosphorylation levels, reduced by exercise, were reversed by anti–IL-6 antibody (Figure 6c and d).

Negative_regulation (reversed) of AMPK

5) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.33 Pain Relevance 0

As previously shown [43], exercise, per se, does not alter AMPK activity in the hypothalamus; however, we observed that the normal inhibition of AMPK phosphorylation and activity in the hypothalamus, induced by leptin administration, was improved in both lean and diet-induced obesity rats after acute protocol of exercise.

Negative_regulation (inhibition) of AMPK in hypothalamus associated with obesity

6) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.30 Pain Relevance 0

Taken together, these data indicate that the anti-obesity actions, induced by leptin, could be increased due to the more pronounced inhibition of the AMPK pathway observed after leptin infusion in the hypothalamus of both lean and diet-induced obesity rats after acute exercise.

Negative_regulation (inhibition) of AMPK in hypothalamus associated with obesity

7) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.44 Pain Relevance 0

Next, we investigated whether the increased sensitivity of the leptin action on food intake induced by exercise, could be due to the modulation of AMPK activity.

Negative_regulation (modulation) of AMPK

8) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.29 Pain Relevance 0

Leptin reduced AMPK and ACC phosphorylation levels in the hypothalami of control and exercised rats.

Negative_regulation (reduced) of AMPK

9) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0 Pain Relevance 0.03

Exercise induces a decline in skeletal muscle malonyl-CoA, which is accompanied by inactivation of ACC and increased activity of AMP-activated protein kinase (AMPK).

Negative_regulation (inactivation) of AMPK in skeletal muscle

10) Confidence 0.25 Published 1997 Journal J. Appl. Physiol. Section Abstract Doc Link 9338417 Disease Relevance 0 Pain Relevance 0.08

In addition, AMPK activity is diminished in IL-6 deficient mice at rest and the absolute increases in AMPK activity in these tissues caused by exercise is diminished compared with control mice [27].

Negative_regulation (diminished) of AMPK

11) Confidence 0.25 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.10 Pain Relevance 0.03

Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect.

Negative_regulation (inhibitor) of AMPK

12) Confidence 0.25 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2585815 Disease Relevance 0.24 Pain Relevance 0.04

Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise.

Negative_regulation (reduction) of AMPK in hypothalamus associated with obesity

13) Confidence 0.25 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2585815 Disease Relevance 0.25 Pain Relevance 0.04

Treatment with leptin markedly reduced food intake, AMPK activity and increased mTOR activity in exercised rats that were pretreated with vehicle, although no increase in response to leptin-induced anorexia and modulation of AMPK/mTOR pathway were detected after i.c.v. pretreatment with anti-IL-6 antibody.

Negative_regulation (reduced) of AMPK associated with appetite loss

14) Confidence 0.25 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.15 Pain Relevance 0

Comparing AICAR treated groups (control vs. exercise), exercised animals showed reductions in AMPK threonine and ACC serine phosphorylation of 52% and 31%, respectively.

Negative_regulation (reductions) of AMPK

15) Confidence 0.24 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0 Pain Relevance 0.03

Comparing fasting treated groups (control vs. exercise), exercised animals showed reductions in AMPK threonine and ACC serine phosphorylation of 65% and 41%, respectively (Figures 3l and m).

Negative_regulation (reductions) of AMPK

16) Confidence 0.24 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0 Pain Relevance 0.03

Overall, perhaps the most striking finding to emerge from our study was that many AMPK activators are inhibitors of mitochondrial function.

Negative_regulation (inhibitors) of AMPK

17) Confidence 0.14 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0 Pain Relevance 0

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