Research Review: Relaxed muscle = slow metabolism?
With a show of hands, how many of you have become obsessed with the Vancouver Winter Olympics?
I see. You’ve watched every heat in speed skating, every trick in snowboarding and every run in downhill skiing! You’ve even watched curling… but that was on The Simpsons.
You’ve watched so much Olympics that when you sleep, you have Tetris-like dreams of frolicking in snow and ice; your body is so confused that it shivers to keep you warm and you wake up in a pool of sweat — damn thermogenesis!
Thermogenesis literally means the making (genesis) of heat (therm).
However, we don’t usually call the furnace repair service and say our heater has impaired thermogenesis (although this might impress or at least confuse them); “thermogenesis” is pretty much only used when talking about the making of heat by a body.
Energy for thermogenesis is only for heat and nothing else – not for maintaining your organs such as your liver and brain (basal metabolic rate) or moving you from point A to point B (physical activity). It’s just for warming you up .
For most people thermogenesis makes up about 15% of the daily calories they burn, but in some cases thermogenesis could be less.
Figure 1 shows how a 5% decrease in energy used for thermogenesis by a person could led to weight gain and possibly obesity. Imagine if you always stored 5% of your daily calories… that means out of a 2000 calorie/day diet, you’d store 100 calories as fat, or about 10 lb a year.
Many moons ago I wrote a blog post about brown adipose tissue (BAT) and how adults actually have some that may help keep them skinny. BAT may be one reason for differences between people’s thermogenic rates, but there is another potential factor – muscle thermogenesis.
Most of you are familiar with the teeth-chattering, uncontrollable shivering, muscle thermogenesis – appropriately, called shivering thermogenesis – but there is another type of muscle thermogenesis, called non-shivering thermogenesis .
And you thought scientists weren’t creative.
Yup, your muscle can just sit there without any spastic contractions and keep you warm, all with the help of an energy source called ATP (basically the battery for all cells in your body) and a protein called ATPase.
There are three types of ATPase in muscle  that use energy and produce heat:
- Na+/K+ (sodium potassium) ATPase is the starter of the muscle cell. This allows electrical signals along the muscle cells without it only the part of the muscle near neurons would contract.
- In physiologese:- Na+/K+ ATPase makes a K+ gradient by moving Na+ out of the cell and K+ into the cell. The cell membrane is permeable to K+, so it leaks out of the cell making a voltage gradient.
- Ca2+ (calcium) ATPase is the cleaner of the muscle cell. It removes the calcium in the muscle cell that is released into the muscle during a contraction. Without it, your muscles would stay contracted forever after you contracted them once.
- In physiologese: Ca2+ ATPase pumps all the calcium that is released by the sarcoplasmic reticulum (SR) during contraction back into the SR.
- Myosin-ATPase is the motor of the muscle cell and uses the most energy. This is what uses the energy during the actual mechanical contraction of the muscle. Without myosin-ATPase, you wouldn’t get any contraction. And by the way, it comes in different varieties: slow, fast or fastest. These correspond to slow (type I), fast oxidative (type IIA) or fast glycolytic (type IIB) muscle fibres.
- In physiologese: Myosin ATPase allows the muscle to shorten by releasing the myosin head from the actin filament.
Myosin-ATPase (or just myosin from now on) is one of the major proteins that contracts your muscle and keeps you warm. Unlike the other ATPases, myosin can make a lot of heat without actually doing anything else. Without contracting it just sits there using ATP and making heat. It’s quite a busy little bee.
This week I review a study that was looking for one thing (how fast myosin can use ATP) and found something much more interesting (myosin may be the key to weight loss).
Stewart MA, Franks-Skiba K, Chen S, Cooke R. Myosin ATP turnover rate is a mechanism involved in thermogenesis in resting skeletal muscle fibers. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):430-5.
To figure out how fast mysosin (ATPase) uses ATP, you need to be able to somehow see ATP being used in a live muscle (or at least muscle cell).
Luckily you can make (or buy) a fluorescent ATP that is not only useful and possibly groovy when the lights go out, but it lets you see the ATP in muscle cells. Even better, you can watch it disappear. The faster the fluorescence vanishes, the faster the myosin is using ATP.
For the fluorescent ATP (2′(3′)-O(N-methylanthraniloyl-ATP)) labelling to work, researchers need to use a technique that sounds like a drinking game — a pulse chase.
First, the pulse: add a bunch of fluorescent ATP to the muscle cell. Sort of like the way that dish soap cuts grease, the lipid-based cell membrane is made permeable with detergent (no, not Palmolive, but close).
Second, the chase: add regular ATP, so that as the fluorescent ATP is used, the fluorescence fades. The rate at which the fluorescence fades shows how fast the ATP is being used by myosin.
Just like a shot of tequila goes better with a little lime chaser, if you don’t chase fluorescent ATP with regular ATP, then the fluorescent part of the ATP will just hang out at the myosin head and the fluorescence won’t fade.
There are a couple things to note:
- Researchers used fast-twitch muscle fibres: a rabbit psoas muscle. That may matter, since myosin comes in different flavours that use ATP at different rates.
- The muscle fibres were relaxed.
In relaxed muscle fibres, myosin takes about 15 seconds to use ATP, which is pretty close to purified myosin; but in what the researchers are calling a super relaxed state, it takes myosin 230 seconds (almost 4 minutes) to use a molecule of ATP.
Let’s talk for a sec about the different myosin types, and how this might be relevant.
Purified myosin doesn’t have anything else. It only has myosin (hence the “purified” label). Thus, the researchers figure there is nothing to inhibit how fast myosin uses the ATP. Think of a four-year-old child in a candy store with no supervision — how fast could that kid polish off a bag of jelly beans? Pretty damn fast – 0.15 seconds per jelly bean (ATP).
Myosin in living muscle is a slightly different story. Living muscle regulates myosin because your body wants to save ATP. Thus the body inhibits the amount of ATP myosin is allowed to consume. We don’t yet know how. (The researchers are still working on that question.)
But basically, imagine that instead of a four-year-old running amok, myosin is supervised by their older teenage brother. The toddler eats the jelly beans (ATP) more slowly (0.20 seconds per jelly bean). The slow jellybean eater is the relaxed myosin.
In the super-relaxed state there is even more inhibition. Now the mother’s watching the four-year-old. So super-relaxed myosin eats the jelly beans (ATP) very slowly – 230 seconds per jelly bean.
Basically what the researchers figured out is why myosin (ATPase) can consume ATP at different rates.
You see, for a long time nobody could figure out why purified myosin used ATP way faster than myosin in living muscle, and why myosin of living muscle seemed to use ATP at different rates.
In this study the researchers think they found the answer: “relaxed myosin” and “super relaxed myosin.”
To be clear, these scientists haven’t figured out how or why there is a difference in how fast ATP is being used. All they know is that there is a difference. And they think this difference could be the Next Big Thing in understanding (and maybe even changing) metabolism.
How fast your myosin uses ATP while relaxed makes a huge difference to how much heat your muscle makes (thermogenesis). That, in turn, changes your metabolism.
- If your myosin is relaxed most of the time it’ll use a certain amount of energy (ATP) to make some heat.
- If your myosin is super-relaxed most of the time, it’ll use a lot less energy (ATP), make less heat and slow down your metabolism.
Now the question is: can you do anything to change how fast your myosin uses ATP? For now, nobody knows. (But it’s a good bet that sitting on the couch with a slanket probably doesn’t help, even if you are watching the Olympics.)
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