You’ve probably never heard of AMP-activated protein kinase (AMPK), yet this enzyme could be an incredible game-changer in treating metabolic disorders and conditions. That’s because the AMPK enzyme is also referred to as the “metabolic master switch.” Let’s take a quick step back …

Our country is in the midst of a health crisis. Heart attacks are far more common than they ever have been, obesity is on the rise, and metabolic-based disorders — a disorder that “occurs when the metabolism process fails and causes the body to have either too much or too little of the essential substances needed to stay healthy” — have taken an uptick. While these are somewhat terrifying realities it has caused a spur of research to delve deeper into the science of our bodies, what makes us tick, and, specifically, how our metabolism works. This is how the AMPK enzyme or “metabolic master switch” was discovered.

While this enzyme promises to have a variety of implications for our overall bodily health, many studies are focusing on the relationship between AMPK and metabolic-disease associated inflammation, diabetes, insulin resistance, and obesity.

Want to learn more! Read further to learn about the AMPK enzyme and what science has to tell us so far.

What is AMP-activated protein kinase (AMPK)?

The AMP-activated protein kinase (AMPK) goes by a few names including the “magic bullet for healthy”, “master regulator,” and the “metabolic master switch.” It’s obviously a hugely important find and cog for our health, but what is it and how does it work?

What are Enzymes?

First off, what’s an enzyme? Enzymes are “biological molecules (typically proteins) that significantly speed up the rate of virtually all of the chemical reactions that take place within cells.” Along with aiding digestion (think about all the chemical reactions taking place to break down food!), enzymes are also incredibly important for metabolism. Plus, they are “highly selective catalysts, meaning that each enzyme only speeds up a specific reaction.”

Basically, they’ve all got their own jobs to do. Enter AMPK!

What is AMPK and How Does it Work?

Adenosine 5′ monophosphate-activated protein kinase (AMPK) is an enzyme — also called an energy sensor — that “sits at the center of a cell’s metabolic switchboard.” Due to its location, AMPK is a crucial mechanism for determining your body’s response to “levels of fuel like glucose or fatty acids.” This metabolic protein has been shown to have “health-promoting effects to reverse diabetes, improve cardiovascular health, treat mitochondrial disease — even extend life span.” It works on what’s called a “downstream effect.”

When the enzyme is activated, it causes “fatty acids to get oxidized in the cell, glucose to be taken up from the bloodstream, cholesterol synthesis to be inhibited, breakdown of lipid stores to low down, inhibition of triglyceride synthesis, and increased sensitivity in insulin release.” Just take a minute and soak that in! Just one activated enzyme can begin this cascade that affects how your body uses and process a variety of compounds.

How is AMPK Activated?

There are a few ways in which AMPK is activated or “turned on.” This is the most important part of AMPK’s magic. Without an activated enzyme, it won’t begin that downstream effect and you can’t reap all those wonderful health benefits. First and foremost, AMPK is activated by energy depletion — “lack of cellular energy” — which “causes more of the protein activated protein kinase (AMP) to be produced.” For you and me, this means that healthily stressing your body with stressors — such as “calorie restriction, fasting, and intense exercise” — can activate AMPK.

When AMPK is activated “in tissues throughout the body,” it begins to alter the activity of many other genes and proteins, helping keep cells alive and functioning even when they’re running low on fuel.” Beyond that, research also stipulates that AMPK may be activated by certain medications. With that said, research is really in its infancy in this arena, so we’ll return to that down the road when more substantial science is available!

Health Benefits of Activated AMPK

Now we know what the enzyme is, where it’s located in the body, and how it works. Alright, but what will it do for our health? Turns out there are actually quite a few health benefits currently associated with the Adenosine 5′ monophosphate-activated protein kinase enzyme. Here are a few of the studied effects of this activated enzyme!

1. Regulation of Energy Usage

While this may seem not very useful, it’s actually a huge part of our overall health. For instance, think about the wildly popular ketosis diet. This diet is all based around your body switching from using glucose (or sugar) for energy to burning fat for energy, which then creates ketones, which offer a wide range of health benefits including more efficient energy use and fat burning.

It all comes down to your hypothalamus and, thanks to Dr. Josh Axe CN, DNM, CNS — a “doctor of chiropractic, certified doctor of natural medicine, and a clinical nutritionist” — here’s a breakdown of the mechanism

“The part of your brain called the hypothalamus is considered your “command center” when it comes to your metabolism. The hypothalamus is a region of the forebrain that coordinates both the autonomic nervous system and the activity of the pituitary gland. It helps maintain homeostasis by controlling energy output, body temperature, thirst, hunger, sleep, emotional activity, hormone production, and other bodily activities. (2) Hypothalamic AMPK restores energy balance by making you want to eat more in order to increase energy intake.”

2. Decreases Inflammation

A highly studied effect of AMPK — especially when it comes to metabolic disorders and chronic conditions — is its ability to reduce bodily inflammation. AMPK has been shown to reduce inflammation by promoting “antioxidant activity, building defenses against factors that accelerate aging, such as a poor diet, chemical/toxin exposure, and chronic stress.” Yet, it’s not just about antioxidants, but also about “signaling.”

The ability for this enzyme to signal — a trait of most enzymes — has been linked to the prevention of “chronic conditions tied to inflammation, such as cardiovascular disease and diabetes,” because of its secondary effects such as “[decreasing] production of fatty acids, cholesterol, triglycerides, and proteins.”

3. Improves Insulin Sensitivity

What’s insulin sensitivity and why do we care about it?

Insulin sensitivity “refers to how sensitive your body is to the effects of insulin.” Depending on how your body reacts to insulin, you may have higher or lower risks for certain conditions such as diabetes. For instance, “those that are insulin sensitive … require smaller amounts of insulin to reduce glucose levels, and, therefore, allow their bodies to quickly process glucose and stabilize blood sugar levels.” Yet, those with a high level of insulin sensitivity are more susceptible to “high blood pressure, osteoporosis, heart disease, cancer, and [may] causes issues in those already suffering from type 1 diabetes.” On the other hand, low insulin sensitivity is a precursor to insulin resistance as it requires “larger amounts of the insulin hormone to control glucose levels and have a more difficult time stabilizing blood sugar levels.”

The activation of AMPK “promotes glucose uptake and utilization,” while also “decreasing glycogen synthesis.” What does this all mean? Basically, these “signaling pathways can increase glucose uptake within muscles so they continue to have a source of fuel,” while also stimulating the “breakdown of glucose for energy in order to form more ATP.”

What Current Science is Saying

Even though there’s a lot of information and data out there about AMPK — in fact, it’s been studied for almost 30 years! — the findings and publication of those findings (as well as the importance in our current health crisis) is somewhat new to the health, science, and medical world. This means that looking deeply at the science is the best way to understand what the AMPK enzyme has to offer (or not offer).

1) Life Extension Magazine, “The Cellular Enzyme That Promotes Longevity and Reduces Fat Storage”

This article is a fabulous place to start! It’s got a wonderfully simplistic breakdown of AMPK, along with easy to follow bullet points, but it also focuses specifically on the enzymes ability to promote longevity and reduce fat storage in the body. It’s also got one of the lengthiest lists of resources, which means the information is well-researched and diverse! Yet, this article is truly great if you’re looking to understand both the health effects and activation of the AMPK enzyme.

Life Extension reports that “by increasing AMPK activation, we can reduce many of the destructive factors of aging, thus enabling cells to return to their youthful vitality.” Specifically, in preclinical research, “enhanced AMPK activity has been associated with a 20-30% increase in life span, but that’s just the beginning of the health benefits conferred by this critical cellular enzyme.” On top of that, “increased AMPK activation has been shown to help reduce fat storage(especially dangerous belly fat), increase insulin sensitivity (to lower blood glucose), reduce cholesterol/triglyceride production, and suppress chronic inflammation.”

Life Extension also reported that there are “two naturally sourced extracts” — Gynostemma pentaphyllum and trans-tiliroside — that may activate AMPK without the need of those bodily stressors such as “drugs, severe calorie restriction, or exercise.”

2) Discover Magazine, “A Master Switch in the Body”

Discover Magazine, on the other hand, focuses specifically on the whole master switch part of the deal.

This article focuses on the “small clump of atoms called acetyl group — [which] may be the most important body process you have never heard of.” So, what does this group do? Firstly, AMPK is part of this group. Secondly, these atoms activate and deactivate “proteins, thereby regulating access to our DNA and [help] control gene suppression.” Now for the science!

One study performed at the University of California at San Diego by biochemist Kun-Liang Guan, “found that more than a thousand of the proteins, including virtually every enzyme associated with metabolism, were acetylated.” What does this mean? This means that “acetylation helps regulate how the body gets its energy” and that by understanding this group of atoms prevention or cure for disease may be down the road. The Discovery article also highlighted biochemist Chunaram Choudhary of the University of Copenhagen, who looked at “human cancer cells and identified 1,750 acetylated proteins, 240 of which also turned up in Guan’s results.” This connection is quite astounding! Chunaram Choudhary explained that “deliberately turning proteins on or off through acetylation may be a simple and efficient approach that offers ‘a good chance of treating some of the worst human diseases.’”

3) Harvard School of Public Health, “A Cellular ‘Switch Could Be Target for Improving Metabolism, Treating Obesity, Diabetes”

Last, but definitely not least, is an article by the Harvard School of Public health which takes aim at how AMPK could affect metabolic diseases, specifically diabetes. The study performed at the Harvard T.H. Chang School of Public Health focused on the “understanding of how brown fat cells works” and their findings landed upon a “molecular switch” also called AMPK. How are these related? Basically, AMPK “turns certain vital processes inside the cells on and off to support the functions of protecting the brown adipose tissue.” This specific study looked at the metabolic relationship between this “molecular switch” and the symptoms of both obesity and diabetes, in which brown fat can play a major role.

Per a senior study author Gökhan S. Hotamisligil, J.S. Simmons Professor of Genetics and Metabolism and head of the Sabri Ülker Center for Nutrient, Genetic and Metabolic Research, “If we can understand these mechanisms fully, we can turn the switch on and off in brown fat cells to help people with metabolic problems.”


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