Wednesday, February 24, 2016

What Effect Does Linoleic Acid Have On Mitochondria?

That's really the key question for metabolic syndrome, for as this paper observes:

"The centerpiece of the pathophysiologic mechanism of metabolic syndrome is insulin resistance. Recently, it is becoming evident that mitochondrial dysfunction is closely related to insulin resistance and metabolic syndrome...." 
"Mitochondrial dysfunction and metabolic syndrome—looking for environmental factors"

Diet is, of course, an "environmental factor".  If linoleic acid (LA) really is the cause of mitochondrial dysfunction, then the solution is quite straightforward.

I found this paper (2011):

"Increased mitochondrial matrix directed superoxide production by fatty acid hydroperoxides in skeletal muscle mitochondria"

The "fatty acid hydroperoxides" (FA-OOH) they're discussing* are all from LA, as the paper makes not as clear as they should.  Since they find that dysfunctional mitochondria have lots of LA hydroperoxides, they're looking to see if that's the cause or an effect.

"...Therefore, the purpose of this study was 1) to determine whether FA-OOH’s alter mitochondrial function (rate of ATP production, RCR [respiratory control ratio] and enzymatic activity of respiratory chain complexes) in skeletal muscle mitochondria and 2) to determine the effect of FA-OOH on the topology and sites of superoxide production, using methodologies that can distinguish between superoxide released towards the matrix and towards the intermembrane space...."

Well that sounds right.  How'd they do?

"...We demonstrate for the first time that low micromolar concentrations of FA-OOH decreases the rate of mitochondrial ATP production, RCR and the enzymatic activity of respiratory chain complexes I and III in skeletal muscle mitochondria. Additionally, using methodologies that distinguish between superoxide generation towards the matrix and intermembrane space, we demonstrate that in skeletal muscle mitochondria, FA-OOH (but not FA-OH [fatty acid hydroxide**]) significantly increases the rate of mitochondrial ROS production directed towards the matrix (and not the intermembrane space) with complex I as the major site of ROS production."

So oxidized LA is bad for your mitochondria, increasing oxidation and decreasing energy production. The relevance of this finding is stated in the discussion:

"Previous studies by our group and others have shown that muscle atrophy is associated with an increase in mitochondrial oxidative stress and dysfunction [2, 7, 47, 48]. Our recent study showed that mitochondria isolated from atrophied muscles generate significant levels of lipid hydroperoxides [19]. However, no studies thus far have investigated the role of fatty acid hydroperoxides in the modulation of mitochondrial oxidative stress and dysfunction in skeletal muscle mitochondria."

They also note that this effect is not limited to just skeletal mitochondria:

"Other studies in heart, brain and liver mitochondria also indicate that fatty acids and fatty acid hydroperoxides are important modulators of mitochondrial respiration and ATP production [8, 11, 12, 49, 50]."

"Modulators" isn't the word I'd choose, but the point is the same.

Now based on the results described in yesterday's post, I wonder if the ROS they're finding directed into the matrix are coming from the cardiolipin itself, and not from complex I or III, as cardiolipin lines the matrix.  But that's kind of an academic question.

"In conclusion, we describe an important finding that at low micromolar concentrations, FA-OOH (but not FA-OH) induces skeletal muscle mitochondrial dysfunction."

So oxidized LA metabolites are the cause.

Since we already know that, in humans, reducing LA consumption reduces the mitochondrial production of oxidized LA, and the symptoms thereof, that seems like a pretty safe recommendation.

And you don't need to wait for a drug.

*Why they're discussing "methyl linoleate" is a mystery to me, but whatever.  Perhaps because that's what the suppliers are selling?  Eating biodiesel seems like a bad idea that even a doctor could understand.  As the results they're describing are consistent with other evidence, I'm not going to delve deeper into that mystery.

** Soap?  Really?  Don't eat soap, even if it's OK for your mitochondria.