AMPK is a kinase enzyme known for its role in metabolic health and cellular energy homeostasis. AMPK is activated during periods where cellular energy levels are low leading to an adaptive response. This is in contrast to MTOR, which is activated when chemical energy is abundant within the cell. [R]

In regards to how AMPK might affect you… it stimulates fat loss, [R] improves insulin sensitivity, [R] decreases inflammation [R] and activates many longevity-promoting and anti-ageing pathways, such as FOXO3, sirtuin enzymes (see more here), NRF2 (here) and autophagy (here). [R1] [R2] [R3]

Effects of AMPK

1. AMPK Increases The Likelihood of Fat Loss

AMPK activation inhibits the synthesis of fatty acids, cholesterol and triglycerides, while also enhancing fatty acid uptake into the cell and forthwith burning of said fatty acids (via beta oxidation). [R]

2. AMPK EFFECTS Glucose / cARBOHYDRATE mETABOLISM

AMPK allows skeletal muscle cells to uptake more glucose via translocation of GLUT4-containing versicles into the plasma membrane (channels that allow glucose into the cell). This is one of the key reasons why AMPK activation is vital during exercise as it allows for sustained glucose supply to muscle cells in the absence of insulin. [R1] [R2]

AMPK also inhibits glycogen synthesis/glucose storage to make more glucose available for usage. Saying this chronic AMPK activation will contrarily increase glycogen storage by massively increasing the abundance of glucose in the cell. [R] Lastly, hypothalamic AMPK enhances glucose production in the liver, presumably via a hormonal mechanism. [R]

3. Ampk Inhibits Protein Synthesis

The production of new proteins is a very energy expensive process and one that is inactivated by AMPK in order to make the cell more energy efficient. In turn, AMPK likely negatively regulates skeletal muscle mass both via inhibiting anabolism (growth processes) and promoting catabolism (breakdown). [R]

4. AMPK Activates Autophagy (Cell Recycling)

AMPK activates autophagy in an effort to increase energy availability. [R] Greek for, “self eating,” autophagy is the degradation of often damaged, useless or misfolded cellular components. [R] Enhanced autophagy has been linked to a variety of positive health outcomes as well as slowed ageing, [R] something I talk more about here.

5. AMPK Triggers Mitochondrial Biogenesis/production and Turnover

AMPK increases the number of mitochondria in the cell in an effort to improve energy efficiency in the future. This is part of the adaptive mechanism to exercise and plays a role in enhancing VO2 max. [R1] [R2]

AMPK also triggers mitophagy, mitochondria-specific autophagy, meaning no unhealthy mitochondria continue to exist within the cell. Maintenance of healthy mitochondria is crucial for longevity and the activation of pro-longevity genes. [R]

6. AMPK Increases Levels of Cellular NAD+ and SIRTiun activation

AMPK, when active, is able to convert nicotinamide (vitamin b3) into NAD+ and sirtuin enzymes are well known for their anti-ageing, pro-longevity effects (see more). All of the sirtuin enzymes are NAD-dependant, meaning that the increased NAD+ levels bought about by AMPK positively regulate sirtuin activity and thus longevity. SIRT1 activation has also been shown to activate AMPK. [R]

7. AMPK activates NRF2

AMPK activates NRF2, which is a master regulator of antioxidant, anti-inflammatory and detoxification genes (more) [R]

8. AMPK INHIBITS INFLAMMATION

AMPK directly suppresses NFkB, a major inflammation regulator, in addition to its weak effects on NRF2. [R]

9. AMPK INCREASES LONGevity

Both dietary restriction and fasting are the most reliable ways to make organisms live longer. [R1] [R2] The longevity effects of these diets are mainly mediated by AMPK [R] and the subsequent autophagy, mitochondrial, Sirtuin, FOXO and NRF2 enhancements already detailed.

10. AMPK eNHANCES iNSULIN sENSITIVITY, iMPROVING dIABETES

As previously stated, AMPK allows skeletal muscle cells to uptake more glucose via translocation of GLUT4-containing versicles into the plasma membrane (channels that allow glucose into the cell). [R] This ameliorates the hyperglycaemia observed in diabetic patients and means that muscle cells require less insulin to get the same amount of glucose, allowing them to progressively re-sensitise to its effects. [R]

11. AMPK Increases Nitric Oxide and Blood Flow

AMPK induces vasodilation in vascular tissues by stimulating nitric oxide release. This has been highlighted as another benefit of AMPK-activators for obese patients, who often experience blood flow issues. [R]

12. AMPK Increases TESTOSTERONE

AMPK increases testosterone levels found in human cells when studied. [R]

13. ampk could Improve Memory

AMPK increases the synthesis of new AMPA receptors, a vital part of new memory formation. [R]

14. Hypothalamic AMPK INCREASES APPETITE

Hypothalamic AMPK mediated many of the feelings everyone experiences when they are hungry. Ghrelin, the hunger hormone, increases hypothalamic AMPK. [R] This is why metformin and berberine are better AMPK activators than AICAR as they do no activate hypothalamic AMPK/ increase appetite. [R1] [R2]

15. AMPK is Anticancer

Ampk has been shown to oppose tumour progression in multiple studies as has fasting. AMPK could also in theory reduce cancer risk via the longevity and anti-inflammatory pathways already detailed. [R]

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