Changing the shape of mitochondria can reverse some of the molecular processes behind obesity (at least in mice)
Do you have a BMI over 30? Welcome to the land of obesity.
It is easy to get there, it is no coincidence that BMI (weight in kg / (height in cm) ²) is a disputed metric. It does not take into account body composition.
For the average person, it's a fairly acceptable quick measure to monitor body composition. However, many strength-working athletes, for example, would be "obese" based on their BMI simply because they have a lot of muscle mass.
A slightly more accurate way of assessing obesity is the accumulation of excess body fat. For men, this is generally considered> 25% and for women> 30% of body weight.
If excessive, of course, body fat increases the risk of various health conditions, such as cardiovascular disease, type 2 diabetes, sleep apnea, various cancers and other things we would like to avoid.
It's not always about food
The causes of obesity are more complex than simply "too much food". Yes, this certainly plays a role, but factors such as genetics, gut bacteria, other diseases, medications, and so on, can also change calories in and / or out.
Obese mitochondria?
The small structures of our energy-generating cells, the mitochondria, also appear to be involved. But let's take a small step back, a little history.
in 1994, the molecular geneticist Jeffrey Friedman discovered a hormone, la Leptin. He wanted to find out why some lab mice became obese (kept eating) while others had no problem maintaining weight (stopped when full). Eventually, he focused on leptin, now also known as the satiety hormone.
This hormone is produced by fat cells and absorbent cells in the intestine. Leptin mostly transmits a message to brain cells in the hypothalamus. The message is: "We've had enough food, we can stop eating."
But if leptin is produced in fat cells, why don't people with a lot of body fat get the message of satiety?
They receive it, but they ignore it. They have lost their sensitivity. Leptin resistance causes their body to ignore the "you are full" message.
Obesity, we now know, is strongly correlated with leptin resistance.
This is why even administering extra leptin (once believed to be the holy grail in the treatment of obesity) doesn't do much. The body simply ignores it.
What Affects Leptin Resistance? The mitochondria.
One factor affecting this leptin resistance is a problem with the mitochondria. A Western-style diet with a lot of saturated fat can cause this problem.
Excessive mitochondrial fission changes the shape of the mitochondria. Normally, the mitochondria are somewhat elongated and tube-like. Fission, however, shortens them, crushes them and makes them a kind of blob. When this happens, their function is impaired.
In summary? Swollen mitochondria equals impaired metabolic function, liver insulin sensitivity, and leptin resistance.
What if we could remodel the mitochondria? A new study he tries.
The researchers used a small molecule (patented, of course), called SH-BC-893. A water-soluble and orally bioavailable molecule. This molecule blocks some of the proteins necessary for the fission of mitochondria.
The administration of the molecule both on obese mice and in Petri cells has shown several things: first of all it prevents the fragmentation of mitochondria. What's more, giving mice this compound reverses obesity-associated alterations in leptin. This molecule reduces food intake and promotes weight loss. It also corrects the metabolic dysfunction caused by obesity.
The conclusions of the study
Our work shows that targeting mitochondrial fission is safe, feasible and effective in a diet-induced obesity model, results that could translate into other human diseases where pathophysiology is driven by fragmentation of the mitochondrial network.
Of course, what's safe and effective in lab mice isn't necessarily safe in humans. We will need to determine both the toxicity profile of the molecule and its efficacy in humans.
In addition, the fission of mitochondria (if it is not so excessive) has its own usefulness. Mitochondria are quite dynamic and regular fission and fusion are necessary to maintain good cellular energy production. They should not be blocked completely.
