Metabolic Syndrome 5 Part Deep Dive Part IV

Part 4 – The Mighty Mitochondria –

Mitochondria started off as a small purple bacterium, then they embedded themselves within another cell to symbiotically work together. Over the next billion years those combined cells evolved to form animals and humans. This ancient bacterium is still within us today and continues to create ATP (the energy we use to survive and thrive). The average human cell has between 1000-2000 mitochondria, and some parts of our body that needs the most energy like the brain, retina and our heart contain about 10,000 mitochondria each. In fact, our entire respiratory system, heart, lungs and blood exist to deliver oxygen to our mitochondria so they can make the energy (ATP) that keeps us alive.

The most important thing your mitochondria do is extract energy from the food you eat and combine it with oxygen, and make ATP. Our body converts sugar (or sometimes protein) into glucose, or it converts fat into ketone body called beta-hydroxy-butyrate (BHB). Both glucose and BHB can provide carbon and electrons, the raw materials that create energy.

Why are we talking about mitochondria you might be asking? Well, Glucose and lipid (fat) metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low and contribute to mitochondrial disfunction. Mitochondrial dysfunction is a central cause of insulin resistance.

We need the mitochondria to be functioning optimally to burn off the fat from the liver and the muscles. Studies have shown that mitochondrial oxidation can predispose someone to ectopic fat accumulation in the liver and the muscles. Gerald Shulman has shown in healthy aging, that mitochondrial function slows, so by the time you are 70-years-old you have a decrease in mitochondrial oxidation by about 30%, compare to a healthy 20-year-old. And this predisposes us to intramyocellular fat accumulation and insulin resistance in the muscles. that’s why as we age, we are more prone to insulin resistance and type 2 diabetes without the presence of obesity. He has also found reduction in mitochondrial oxidation associated with intramyocellular fat accumulation in young lean IR offspring of parents with type 2 diabetes, suggesting there may be a genetic basis for this abnormality.

To be metabolically flexible, healthy and have well-functioning mitochondria, we are able to go from burning fat to burning glucose when we need to. To see how this works in practice we can look at the work of Dr. Inigo San Millan, the Director of Exercise Physiology at the University of Colorado and a professional speaker on the topics of sports medicine, metabolic disorders and other types of health and performance issues.
His approach is, if he wants to help people with metabolic issues like MtS with the worst functioning mitochondria, he looks at those humans who have the best functioning mitochondria on the planet to see what they are doing and why their mitochondria function so well. And these athletes he looks at are professional cyclists.

One way he assesses a client to see how well their mitochondria are function is to measure their fat oxidation rate during exercise, as it provides an indirect method to assess metabolic flexibility.

He did a recent study assessing metabolic flexibility in three populations to determine how much fat was oxidised under a given exertion of effort.
Fat oxidation ability was significantly higher in professional athletes compared to patients with metabolic syndrome.

At rest normal metabolism burns more fat than glucose, and as the intensity of the exercise goes up, we go from burning fat to glucose and lactate levels raise.

People who are not metabolically flexible, rely on glucose earlier on in the process.

The measurement they use is respiratory exchange rate (RER), at rest in people with normal metabolism their RER remains below 0.7. When 100% of fuel source is glucose the RER is 1.00. Higher RER at low work load, or at rest is a red flag for mitochondrial dysfunction. Metabolically sick people may have their number at 0.9+ while at rest (burning mostly glucose and virtually no fat). (12)

As I mentioned before, skeletal muscle is the first tissue where insulin resistance starts, and about 80% of all the glucose (carbohydrates) that we oxidize in the body after a meal is in skeletal muscle.
In well trained athletes, they have 3x-4x the number of mitochondria and each mitochondria are larger compared to the normal individual.

Cardio vascular training in a specific range stimulates different pathways for mitochondria biogenesis as well as improves the efficiency of the mitochondria. Inigo says that the best treatment is zone 2 training (cardio training in a specific zone) to adapt and improve mitochondrial function. “What I have been seeing for 25 years, working with elite athletes, is that this [zone 2] is the exercise intensity where I see the biggest improvement in fat burning and the biggest improvement in lactic clearance capacity. Therefore, that means that the mitochondria is where you see the biggest improvement. We also see the biggest improvement in performance.” – Iñigo  San Millán, Ph.D.

MtS patients utilize more glucose for energy, and they can’t synthesize fatty acids for energy purposes very efficiently, so they rely on glucose at rest more than the average person.

Now we are getting somewhere! There is a connection between aerobic fitness levels and training, and mitochondrial function. And we can see that represented in the athlete and the MtS patient and their mitochondrial function. And we know MtS patients have more muscle fat and can’t utilize fat as a fuel and utilize glucose more than an athlete. So, lets look at what a single bout of exercise can do with insulin stimulated muscle glycogen synthesis.

This is an indication of the opening up of the road block. Shulman did another more recent study in a similar population.(14)

they showed that the same ingested glucose would lead to more glucose deposition as muscle glycogen, and a significant reduction de novo lipogenesis (making fat out of glucose) and a significant reduction in liver triglycerides. A single bout of exercise prior to two carbohydrate-rich meals resulted in an approximately threefold increase in muscle glycogen synthesis and a 30% decrease in de novo lipogenesis in the liver.

In the next and final article, we will go through some strategies to start reversing MtS and how you can become more metabolically flexible. When you’re more metabolically flexible fat won’t build up in the wrong places, your lipid profile will look better, your blood pressure can even go down to normal, and you can actually start to lose weight! This is exciting, and I hope you’re still reading on and ready to make some life changing choices.