Metabolic efficiency is more important than mitochondrial quantity

It has been hypothesized that insulin resistance in patients with impaired, or diabetic glucose tolerance, is mediated by a deficiency of mitochondria in skeletal muscle. But it turns out that it’s not necessarily the case.
This is because type 2 diabetics and insulin-resistant individuals, with impaired glucose tolerance, have ≈30% less mitochondria and 38% lower mitochondrial density than insulin-sensitive controlled subjects. This phenomenon has also been referred to as mitochondrial dysfunction.
So, based on that hypothesis, it would make sense to increase the number of the mitochondria in order to restore metabolic efficiency and also insulin signalling.
One way of doing so is to activate peroxisome proliferator-activated receptor delta (PPARδ), which will increase PPAR γ coactivator 1α (PGC-1α), and in turn increase mitochondrial biogenesis. Natural activators of PPAR are linoleic-, gamma-linoleic- and arachidonic acid. So it’s basically PUFAs. Eating PUFAs will increase PPAR, which will increase the mitochondrial number.
Muscle carnitine palmitoyl transferase 1 (CPT-1) expression is regulated by PPARδ in skeletal muscle. CPT-1 is the enzyme that transports fats into the mitochondria to be used by beta-oxidation. So PPARδ will also improve fat burning.
The following findings are based on this rat study right here:
The researchers fed the rats a high PUFA diet, one consisting of flaxseed oil and olive oil (high omega 3 and monounsaturated fat) and another of lard and corn oil (high omega 6), along with their other foods.
Sure enough, the high fat feedings increased mitochondrial number, but their conclusion was:
“Because the high-fat diet-induced increases in mitochondria and in the capacity to oxidize fat occurred during the period in which insulin resistance developed, the muscle insulin resistance is clearly not due to mitochondrial deficiency.”
Not only did the high PUFA feeding not improve mitochondrial efficiency, it also induced skeletal muscle insulin resistance and increased circulating free fatty acids. All of this happened in just 4 weeks for both the omega 3 and 6 group. They were strong on their way to glucose intolerance and dyslipidemia. What’s worse is that PUFAs increase insulin sensitivity to adipose tissue and speed up fat gains, compared to saturated fat. And yes the rats on the high PUFA diets did gain more weight than the control group.
However, the researchers stated that:
“Feeding rats the high-fat diets for 4–5 wk was not sufficiently long to result in a significantly greater increase in body weight than occurred in chow-fed controls. However, the omental, epididymal, and retroperitoneal fat depots were significantly greater in the high-fat diet-fed groups than in the chow-fed group (7.7 ± 0.5 g vs. 12.2 ± 1.1 g, P < 0.01).”
They also said:
“Actually, the rate of substrate oxidation in resting muscle is not determined/limited by mitochondrial oxidative capacity but by the rate of ATP breakdown/ADP formation, which is regulated by the cells’ need for energy”
But this is for the next article. Clue: It has to do with PUFAs, reactive oxygen species and cardiolipin.

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