What is AMPK?
Adenosine Monophosphate-Activated Kinase or AMPK is an enzyme which gets activated when the level of your cellular energy drops down, for instance, when you are dieting. It gets regulated by the glycogen present in your muscle tissues when you focus more on them. It has been proved through various researches that this enzyme gets activated when the level of glycogen is slightly low but if it is high then it can inactivate AMPK. Moreover, the presence of certain other hormones in the bloodstream like ghrelin and leptin can also activate this enzyme.
How is AMPK activated?
The fat cells in your body release Leptin and ghrelin hormones depending upon the number of calories you are taking in. The appearance of satisfying hormone Leptin decreases the level of AMPK in your brain whereas the hunger hormone Ghrelin increases the level of this enzyme. In other words, the level of leptin will be high and AMPK enzyme is inactivated when your calorie intake is surplus and you feel full but when you are hungry or lack calories then the level of ghrelin will be high and activates the enzyme.
Working of AMPK
A number of cellular control operations in your body involve AMPK. It plays a vital role in improving the metabolism of carbohydrates, protein, and fat.
Carbohydrate metabolism: When AMPK is activated it slows down the storage and increases the consumption of glucose and increases the sensitivity of insulin. You will be able to use more carbohydrates if you have more sensitive insulin which will also help in reducing your fat. So, for this reason, many drugs used for treating type-2 diabetes include this enzyme as the main ingredient.
Protein metabolism: As activated AMPK improves the metabolism of carbs and glucose it also improves the metabolism of protein. It suppresses the synthesis of protein by deregulating an enzyme, the mammalian target of rapomyacin (or mTOR), which is highly involved in the growth of muscles.
Fat metabolism: The synthesis of cholesterol and fatty acid in the muscle cells and liver decreases with the activation of this enzyme as it increases the oxidation of fatty acid. By stopping the synthesis of new fat your body starts burning the fat accumulated in it. But it is not easy to say that this enzyme helps in losing fat or not as it also decreases the burning of fat in the fat cells.
Other benefits of AMPK activation
- Bodybuilding exercises: Short term benefits are provided by acute endurance exercises like oxidation of fatty acid in skeletal muscle and increased consumption of glucose. This oxidation of fatty acid can result in skeletal muscle adaptation if continued for a long time by changing the transcription of workout responsive genes. These adaptations can increase the rate of production of ATP, a source of energy, by skeletal muscle to sustain exercise. AMP activation plays a great role in these adaptations by maintaining the levels of ATP to their maximum for the survival of a cell. So when the body of bodybuilders is low on energy then it activates this enzyme to maintain the level of ATP along with preventing muscle building and burning fat to create and conserve energy.
- It burns as well as produces sugars: The main source of energy for the normal activities of your body and brain is glucose. When the blood glucose drops below the normal level due to any health condition like Hypoglycemia, it becomes dangerous for the proper functioning and stability of your brain. In such condition, AMPK gets activated to increase the production of glucose by the liver and its consumption by the muscles. This enzyme provides more glucose to your body as it slows down its storage. It also stimulates the breaking of glucose in various cells to gain energy.
- It burns fat: This enzyme slows down the production of cholesterol, triglycerides and fatty acid and stimulates the breakdown of fat when activated.
- It slows down the production of protein: During the state of low energy, your body produces less protein to conserve energy, as it is an energy consuming process. In other words, AMPK slows down the production of protein. But when protein production is slowed down excessively then it can result in wasteful and more energy efficient cells.
- It increases renewal of cells: The process of recycling of cellular compounds in known as Autophagy, which promotes the quality control of subunits of cells and molecular subunits by degrading damaged mitochondria and misfolded proteins. With the help of APMK, this process also helps in the generation of energy by fuelling mitochondrial metabolism.
- It produces new mitochondria: Long-term and acute improvement of mitochondrial activity also depend on AMPK as this enzyme also controls its production. The performance of muscles and activities of mitochondria get reduced with the loss of this enzyme.
- It works as an antioxidant: This enzyme plays a crucial role while controlling oxidative stress by increasing the production of certain antioxidant proteins like superoxide dismutase, uncoupling protein 2 and NRF2 etc.
- It helps in the delivery of Oxygen: This enzyme can also protect you when breathing is acutely unstable while sleeping or at high altitudes where the oxygen level is low. Several types of research on mice have shown symptoms of breathing dysfunction during hypoxia due to loss of AMPK. People at high altitudes at low oxygen areas survive due to the presence of components of this enzyme in their genes.
- It improves fertility: By increasing the production of sex hormones in both the sexes of several animal species it improves their fertility.
- It increases blood flow: By widening or vasodilatation of your blood vessels by releasing stimulated nitric oxide in them AMPK also plays a great role in increasing the flow of blood in them.
- It is beneficial for athletes: Activated AMPK can be beneficial for some exercises to some extent. It has been proved through researches on mice that it use on inactive mice for 4 weeks showed similar benefits as obtained by endurance exercises.
- It improves weight loss: This enzyme can improve the possibilities of weight loss by increasing the burning of fat. You will have to activate it in your liver, muscles and fat and slow down it in the hypothalamus to lose weight effectively. In other words, it helps in decreasing your hunger, storage of energy and increase the burning of stored fat simultaneously. When the activity of this enzyme in the hypothalamic region or brain is slowed down in mice they lose weight by starting eating less than ever. The hormone of this hunger stimulates this enzyme in your hypothalamus. In this way, it also helps in reducing the effects of obesity caused by the certain disorder.
- Its anti-aging effect to increase your lifespan: While aging the level of AMPK activation gradually declines. This loss of the level of an activated enzyme can be due to increase in the level of age-related chronic inflammations. This enzyme can promote the concept of healthy aging with the help of various longevity treatment methods. According to various studies on fruit flies, rodents and worms have proved the crucial role of this enzyme in increasing longevity and lifespan induced by calorie restrictions by at the most 15%. It can also increase your lifespan due to improvement in autophagy and reduction in the production of protein.
- It decreases inflammation: AMPK works reciprocally with inflammation as it reduces inflammation and also gets reduced by it by applying its potent anti-inflammatory effects. By inhibiting NFkB, the main thing causing inflammations, AMPK can slow down inflammation effectively. Though it can reduce the effect of chronic inflammation in such states it can also get reduced I typical cases.
- It improves diabetes: This enzyme can improve the sensitivity of insulin along with improving the glucose tolerance as shown in the studies of mice. An activator of the enzyme, Metformin, is usually prescribed to type-2 diabetic patients along with anti-diabetic drugs.
- It protects from heart problems: This enzyme also helps in protecting you from various cardiovascular problems when activated.
- It increases testosterone level: It can also increase male hormones or androgens in human sex cells. Women with PCOS, a condition with a higher level of male hormone, are usually prescribed metformin, an activator of this enzyme.
Negative effects of AMPK
Two proteins, important and beneficial for the functioning of the human body, PPAR alpha, and PPAR gamma can be suppressed by AMPK which can show harmful effects in various conditions like:
Neurodegenerative disease: When it comes to studying the effect of AMPK on neurodegenerative disease many studies have shown contradictory effects of this enzyme as sometimes it shows contributory properties and sometimes protective. The activated enzyme in the form of metformin has shown an increasing level of amyloid-beta protein in mice with Alzheimer which a contributory effect to the disease. But in AMPK deficient mice increased generation of A-beta was also observed and its activation by AICAR and resveratrol has also decreased the secretion of A-beta. In fact, this enzyme was also associated with increased risk of Alzheimer in obese people with type-2 diabetes when it is inactivated.
AMPK activation in mice with Hintington’s disease has also promoted brain decay and neuronal loss. But according to another study, survival time in rodents with this disease can be prolonged for a considerable time by treating them with metformin. It has also shown in various studies on flies that genetic activation of this enzyme can protect from a neuronal loss in Parkinson’s disease.
Cancer: AMPK has a complicated effect on cancer. It can protect from initiation of tumor and damage to DNA caused by oxidative stress when activated. It also inhibits mTOR which is its anti-cancer feature. But on the other hand, it also increases the consumption of energy and glucose which can be used in the formation of tumors. In this way, this enzyme can be preventive for cancer but not curative. Moreover, it can be used to treat existing cancer by slowing down the effect of adaptation of tumor stress when it is inactive or inhibited.
Ways to the natural increase in AMPK level
If you are suffering from weight issues then you may be interested in increasing the level of AMPK in your fat, liver and muscle cells but decrease in your hypothalamus in a natural manner. How?
Calorie limitation: It is a known fact that limitation on calorie can have many positive effects on your diabetes, cancer, and aging. AMPK intervenes in some of these effects as various mechanisms used in calorie restriction can activate this enzyme. The activity of this enzyme decreases in obese people as it slows down with overeating. It also slows down with high levels of amino acids and glucose as well as elevated insulin and excessive consumption of saturated fat. By limiting calorie intake the secretion of adiponectin from fat cells gets stimulated which in turn activates this enzyme in various tissues like skeletal muscles etc. The secretion of adiponectin also helps in reducing obesity to a great extent due to a partially reduced activity of this enzyme in those people.
Exercise: During exercise, the energy is used in the form of ATP which stimulates AMPK due to loss of energy. The contraction of the muscle during high- intensity exercises also help in activating this enzyme in the human body. This enzyme also helps in providing a number of benefits to the people doing exercises regularly like increased sensitivity to insulin etc. This enzyme can also improve the performance of your muscles due to its effect on the production of new mitochondria.
Cold Exposure: The activation of AMPK can be increased in the hypothalamus and food intake can be stimulated by exposing to cold.
ALA or Alpha Lipoic Acid: AMPK can be activated in muscles and other tissue with the help of this acid whereas it reduces food intake and its activity in the hypothalamus.
Decrease inflammation: inflammation has two-way effects on AMPK as both can reduce the effect of each other according to different conditions. This enzyme can be suppressed by pro-inflammatory cytokines whereas anti-inflammatory cytokines can activate it. It can increase insulin resistance in chronic inflammation whereas increased inflammation can reduce the activity of this enzyme.
In this way, AMPK is an enzyme that can boost your energy level when you need it.
Sol Ruiz heads our Research Digest department. He graduated from the New York University where he obtained his Master’s Degree in Public Health.