Why Exercise Is a Cure-All.

Irisin - A Missing Link

I know it’s been a long time since my last post. I’ve been traveling a lot the past  few months with a lot of time off the grid – which is pleasant but not conducive to doing online research and posting!

In that time I came across some very cool new research results that I’m excited to share. As you probably sense from many of the blog topics, I’m a big fan of exercise – in just about any form and intensity level. The data are numerous and almost uniformly supportive of its benefit in improving long term health.

If you’re like me, you’ve got to wonder, how can an activity like exercise, hit so many systems that are not the muscles actually doing the work ? Read on, and you’ll have a better idea.

in 2012 a research team at the Dana-Farber Cancer Institute and Harvard Medical School were investigating how exercise caused white fat to brown. For those of you unfamiliar with brown fat, this video gives a quick overview.

If you’re a Huberman fan he goes into a lot more depth.

Exercise physiologists have known for a long time that exercise increases the amount of brown fat we have. The Harvard team wanted to know how.

A little background: exercise ups the energy output from your muscle cells. No surprise here. That energy is supplied by the cellular powerhouses called mitochondria. I’ve talked about these in past posts on exercise, muscles, and metabolism. When mitochondria are active, they release a protein called  PGC-1α. It stimulates the production of more mitochondria, but for our story, it also turns on a gene called irisin. The protein encoded by this gene is called FNDC5 (fibronectin type III domain-containing protein 5 if you really want to know).

The Harvard group showed that when muscles are exercised, they release a piece of the FNDC5  protein later named irisin. Here is our missing link in the exercise/benefit story. In other words, exercise releases a hormone-like molecule (irisin) that has effects beyond the muscle.

Inside your muscles, irisin plays several important roles. As you may have guessed, it contributes to muscle fitness. First, it provides the impetus to convert white fat to brown fat. We store some energy in our muscles in the form of fat. Second, irisin turns on a bunch of genes that regulate mitochondria, and probably make them run more efficiently which would improve endurance and reduce fatigue during exercise. Finally, irisin appears to be involved in muscle hypertrophy, or growth, which would increase one’s strength after exercise.

Of course I’m fascinated by the action of irisin in muscle, but its extracellular actions, akin to those of hormones, are really compelling, in part because that can help explain the plethora of benefits exercise confers. One of the most intriguing areas is its potential for brain health.

First, irisin seems to protect neurons by reducing inflammation which is a big player in neurodegenerative diseases such as Alzheimer’s disease. Chronic inflammation is a hallmark of Alzheimer's disease, so irisin’s anti-inflammatory properties probably retard the progression of Alzheimer's. It also suppresses the activation of microglia, the brain’s resident immune cells, thereby reducing the inflammatory response that contributes to neuronal damage in AD. 

Some studies have shown that irisin can stimulate the production of brain-derived neurotrophic factor (BDNF), a protein involved in neuroplasticity, memory, and learning. Because of its potential effects on BDNF, irisin may help enhance cognitive function and memory. (In a previous post on GABA and intermittent fasting, I talk more about the role of BDNF.) Exercise, already known to improve brain health, could be acting via irisin here. Interestingly, these effects of irisin are most pronounced in the hippocampus, the primary memory center of the brain. 

Finally, irisin can reduce the accumulation of amyloid-beta or modulate its toxicity. These amyloid-beta plaques are a central feature of Alzheimer’s pathology. This could be one of the mechanisms by which irisin exerts neuroprotective effects, preventing the neurodegenerative changes typically seen in AD.

There is also some evidence suggesting that irisin may have a role in mood regulation, as exercise is known to have antidepressant-like effects, possibly through irisin's action on the brain.

Given all the preceding upside to irisin, it’s not surprising that it has generated a lot of interest as a molecule that could potentially be harnessed to improve physical health and brain function. That is far in the future however. What you can do today to harness its benefits is keep on exercising!