Uncoupling Proteins - Sometimes a Calorie is Not a Calorie

July 03, 2022

Uncoupling Proteins - Or A Calorie is Not Just a Calorie

"A calorie is a calorie is a calorie". You have heard this bored into your head a thousand times. You don't believe it. And you are right. You can't lose weight and you are certain "Something is amiss." It is. Sometimes a calorie is much, much less. I'm serious. If it gets "uncoupled", you turn calories into HEAT instead of ATP energy molecules. And that makes some calories about 70% of a calorie. Put another way, you can make yourself burn 30% of your calories by how you conduct your life. Want to learn more? But if you can't uncouple, you are stuck with a metabolism that won't give anything away.

Now, remember, you make your body weight in ATP molecules every day, Your mitochondria, (10% of your body weight) turn the low energy molecule ADP (diphosphate) into ATP, (triphosphate) and that is the universal energy molecule for all your cells. Your mitochondria can make 38 ATP from a single glucose molecule. And out comes CO2 and water in exchange. And each ATP molecule gets regenerated some 10,000 times a day.

There are some challenges your body must face that no one ever really put together. What happens if you are a newborn with a huge body surface area to volume? How do you keep that little tyke warm? What happens when you have a lion charge you and you have to go from sitting to sprinting a 10-second 100-meter dash? What do you do if you just stuffed yourself with a feast and are just bloated with turkey and dressing, sweet potato pie, and cheesecake, and ice cream.....? Each of those circumstances requires massive, rapid changes in your metabolic pathways. Each of them involves uncoupling. We'll explain.

Your mitochondria are what you have to respond to that challenge. They must take a resting muscle to a sprinting runner in 1 second, increasing their output by some 40,000 fold. They can do that. But they also need a release valve, almost like a steam engine that lets steam out of the system. That's called uncoupling. You make heat instead of ATP. Your body needs to learn how to do that.

For all that to happen flawlessly and rapidly, we need to have some metabolic pathways in place, working fluidly. One of the most important pathways that needs flexibility is the ability to flex-fuel from glucose (carbs) to fat (many kinds). Your body defaults to running on glucose anytime glucose is around. That's because glucose used to be rare, showing up only once a year during fruit season, or the rare finding of honey. Repeat that. Glucose, for most of human history, was not the default fuel, eaten three times a day. It was rare. The rest of the time, our food was green leaves (think spinach and dandelions, broccoli and kale) or animal products. Green plants get fermented by your colonic biome to make short-chain fatty acids, most notably beta-hydroxybutyrate (a ketone). Fat gets used up, but only after all glucose stores are depleted. If glucose is around, you put out insulin and store any excess calories as fat. That makes insulin your storage hormone that prepares you for winter by storing excess glucose as fat.

Now, with the discovery of agriculture and growing grains just 7,000 years ago, we have carbs year around. With modern farming, we have carbs and sugar at our fingertips 24/7. Hence our metabolism is always running on glucose. Without any demand to burn fat, the enzymes that chop up and prepare fat for our mitochondria are not needed. If not needed, we don't ask our DNA for them to be made. Our peroxisomes, those little organelles next to our mitochondria that chop up fat to present to the mitochondrial furnace, are diminished. They don't have enough to do. Our mitochondria keep getting glucose because we keep eating every day, every 8 hours, and snacking in between. If you go on a diet, and you are glucose addicted, your peroxisomes will not chop up fat and make beta-hydroxybutyrate for you. You become hypoglycemic and feel awful. Your diet fails.

This is a journey that will take you a few weeks to master. I want you to understand how to uncouple your mitochondria and turn on uncoupling proteins. But to do that, you have to start with the basic mechanics of how your energy flow works.

That we feel hypoglycemic when we don't get our regular carbs is another clue. But when you heat a huge meal like Thanksgiving and find yourself hot and sweaty at two in the morning, you are demonstrating uncoupling. That heat is coming because your mitochondria are getting way too many calories thrown at them all at once. They can't manage the overload and to let the steam out of the system, they pull out UCP3, uncoupling protein 3, and say "Let er Rip" and just waste a ton of calories in heat instead of metabolizing it in a proper, orderly fashion. You do gain weight from that dinner, but the heat you felt at 2 am was the even more weight you would have gained had not your mitochondria been uncoupled. The reason for doing that is complex. We'll explain.

Isn't this interesting? Don't you want to know more? We'll get to it next week. This is enough for this week.

www.What will Work for me. This is the fourth of July. You don't want to eat so much that you feel like a furnace and get all hot at 2 am. If you do feel that way, recognized the warning sign. Your mitochondria are begging you to please, not overload the system too fast with so many calories. I'm fascinated with this uncoupling idea. The best way to get yourself able to uncouple is to first get your mitochondria responsive to fat and glucose. The way to start doing that is to let yourself burn off all your carbs every day. To do that, you have to go at least 12 hours without eating. That's when ketones will start to show up in your blood. (You can prove it to yourself by buying a ketone meter from Keto-Mojo and measuring your ketones. After 12 hours of no food, you will have 0.1 mg beta-hydroxybutyrate in your blood. Your peroxisomes are beginning to burn some fat. Now, extend that to 13 hours, then 14, then 15....by the time you get to 18 hours, you will have accomplished step one in getting yourself to uncoupling. Your peroxisomes have "petitioned" your DNA to provide the programming to make fat chopping enzymes. You are making ketones, and they are the key. We will explain that next week.

References: Wikipedia, Frontiers Physiology, PNAS, Circulation, PLOS One,

Pop Quiz

1. What is the best sign that you are carb addicted and unable to make ketones?                       Answer: You get hypoglycemic and feel woozy when you go more than 4 hours without food. The woozy feeling of hypoglycemia is your brain complaining because it is metabolically unable to make and run on ketones. It needs to be trained to do so. And that is possible.

2. What happens when you flood your mitochondria with too many calories all at once (like a milkshake, hamburger and large fries)?                               Answer: Pay attention. You feel sleepy and you feel hot. That hot feeling is uncoupling. Adrenaline will also turn on uncoupling. So when you are embarrassed and your face flushes and you get all hot.......there you have it.

3. What is uncoupling of mitochondria?                                 Answer: The letting off of excess calories into heat instead of ATP to escape the calorie overload.

4. How much of my metabolism can I affect by uncoupling?                              Answer: About a 30% swing if you believe the animal research.

5. You mean that a calorie is sometimes only 70% of a calorie?                       Answer: Yup.