Long-Term Cigarette Smoke Exposure and Skeletal Muscle Mitochondria
I haven’t written a post in a while — mostly because I’ve been swamped writing other things (grants, papers, dissertation, etc.). During that time, I finally published my first first-authored paper, which I will discuss here. You can find the full article, titled Skeletal muscle mitochondrial adaptations induced by long-term cigarette smoke exposure, on the AJP Endo & Metab website (or contact me).
The Why
If you hadn’t already guessed from the title, this paper investigates the long-term effects of cigarette smoke on skeletal muscle mitochondria. Now, the article's point isn’t to argue that smoking isn’t bad or anything; smoking is indeed very, very harmful to health — facts. However, while it’s pretty well-established that persons with COPD generally display a bit of muscle dysfunction — especially mitochondrial dysfunction — it’s been relatively unclear whether the dysfunction is due to cigarette smoking itself or a secondary consequence of physical inactivity. Compared to the general population, people with COPD tend to be more inactive, resulting in muscle dysfunction in itself — hence the chicken or the egg conundrum we have here.
Why does this matter? Well, people with COPD also tend to have a higher prevalence of frailty compared to individuals without COPD, often due to, in part, muscle dysfunction. Since frailty is a predictor of death, it would hopefully benefit individuals with COPD if we identify the cause of this frailty and muscle dysfunction and later produce some treatment. If the dysfunction is, in fact, due to smoking/COPD itself, then the mode of treatment would likely be very different than if this dysfunction were only related to exercise itself. In other words, if:
Smoking → Muscle Dysfunction → Frailty → Hypothetical Treatment 1
Smoking → Sedentary Activity → Muscle Dysfunction → Frailty → Hypothetical Treatment 2
Follow me?
The last bit I’ll say here is that while the obvious answer to all of this is not to smoke, it really isn’t that simple sometimes. Flight attendants (before the FAA ban on in-cabin smoking) and several populations developed COPD even though they never lit a cigarette for themselves. Furthermore, while smoking is the most common cause of COPD, even environmental pollutants can cause COPD. Therefore, this is still worth investigating.
The How
TL;DR
We put mice in a cage and lit up cigarettes so that the smoke produced from said cigarettes was directed into the cages, where the mice would then breathe in the smoke. This was done for 8 months (!!), the longest (to my knowledge) for this kind of study and is equivalent to a few decades of smoking. The mice were also housed without running wheels, eliminating the physical activity component and the conundrum that I pointed out earlier (we can’t really do that in humans, hence mice). We then took muscle samples and measured a few things related to muscle mitochondria (and other unpublished variables), like protein expression and mitochondrial respiration (think ATP production).
Results
The bad
It turns out cigarette smoking does a lot of damage to the muscle. Our mice exposed to smoke had a lot of oxidative stress and damaged proteins, as indicated by increased 4-HNE.
The mice exposed to smoke also had lower expression of myosin heavy chain proteins (the proteins that allow the muscle to contract), which probably played a significant role in the weight reduction compared to the control group. Also, almost all mitochondrial proteins were lower in the smoke group. All of this is no bueno.
The not so bad
Despite the indicators of protein damage and lower expression of mitochondrial proteins, there weren’t any changes to mitochondrial function or content.
It’s a little strange, considering the huge significance in what we saw with the other variables. But, it is what it is!
What it means
First, it means we have more work to do (hello, dissertation!).
Second, I think there are a few ways to interpret these data:
- Exercise is the predominant force in the development of COPD-related muscle dysfunction.
- Cigarette smoke impacts a lot of things in muscle, just not mitochondria.
- Smoking impacts everything in muscle, but the muscle somehow can compensate for these impacts.
- [Insert your thoughts here]
I tend to go with idea #3 the most. It’s clear that everything we measured here (and more) is impacted by cigarette smoke itself. However, this didn’t lead to any changes to the mitochondria. I tend to think that the loss of mitochondrial complexes (which may or may not lower respiration, it’s complicated) and the [potential] loss of mitochondrial function was offset by decreases in uncoupling proteins (UCP3) and the ATP/ADP transporter (ANT). The loss of these proteins resulted in no net change to mitochondrial respiration due to more efficient mitochondria (via UCP3 loss) and less ATP/ADP flux (via ANT). However, this is speculative since we didn’t measure any of these parameters directly. Womp womp.
Nonetheless, these are certainly interesting findings. Perhaps my dissertation will lead some further interesting insights.
