What are Dysfunctional Mitochondria?

The confusion with this whole mitochondria-based theory of obesity continues.  I'm not sure what's driving this other than a desperate clinging to the notion that one's obesity can not be the result of one's overeating and/or sedentary lifestyle, however they came about.  The more I read on this the more bizarre it all seems, but it comes down, once again, this notion that "fat burning" is related to fat accumulation or loss.  This is nonsense.  If your body requires 2000 cal/day to meet energy needs, it's pretty much all the same to your body where it gets that energy from.  And it will always be getting its energy from some mix of substrates:  glucose, fatty acids, and yes, amino acids and ketones.  Nobody disputes that energy is partitioned and substrates are oxidized in different manners largely at the direction of hormones ... insulin and leptin having well characterized roles in this regard.

Somehow, however, low carbers seem to be hijacking the "dysfunction" part of "mitochondrial dysfunction" to mean the opposite of what it is generally accepted to imply.  Can we all agree that our mitochondria deteriorate with aging?  What also happens with aging (absent intervention) as regards mitochondrial function?  Respiratory quotient, RQ.
Basal energy expenditure
elderly: 1489±42 young: 1660±79 kcal/24 hours P=0.055
Respiratory quotient
elderly: 0.74±0.01 young: 0.78±0.02 P=0.059
Glucose oxidation
elderly: 0.65±0.19 young: 0.96±0.19 mg/kg LBM/min P=0.33
Fat oxidation
elderly: 0.98±0.09 young: 0.93±0.19 mg/kg fat mass/min P=0.82
I think the variability here in conjunction with relatively small sample size (16 elderly, 13 young) led the first two observations to be "tending" (they just miss the P<0.05 threshold for statistical significance) and no statistical differences for the other parameters.  I included the glucose and fat oxidation, however, as they do tend to show a trend.  That being there's really not much difference for fat oxidation, but the decline appears to be due to a rather significant (in magnitude) reduction in glucose oxidation rate.  This is also consistent with the results of Resting Metabolic Rate and Respiratory Quotient in Human Longevity, blogged on here.  They found:  respiratory quotient (Rq) displayed an age-related decrease (P < 0.001).  However when those who declined metabolically died off, the RQ was high (though lower than in middle-aged adults).   Therefore the dysfunction resulting in any derangement is by all indication an impairment of mitochondrial glucose oxidation, not in the mitochondrial capacity to oxidize fatty acids.

This is where this whole theory falls apart.  Because somehow the "preobese" have impaired fatty acid oxidizing ability which magically returns with a vengeance once the person becomes obese?  And once the obese has lost weight -- fairly inarguably a healthier state -- we're to conclude that the resting RQ again shooting through the never-obese level (in one study, but not in others) is indicative of some sort of damaged metabolism and mitochondrial dysfunction?  Put another way -- if "fat burning" is the benchmark of mitochondrial health, then we are to believe that the obese have the healthiest mitochondria of all!  Does that make any sense to you?  Me either.

The Rogge study, The Role of Impaired Mitochondrial Lipid Oxidation in Obesity, is providing a lot of blog fodder lately.
In obesity, the excess lipid accumulation represents a surfeit of energy, but those who are obese often experience rapid fatigue and decreased physical endurance, reflecting an energy deficiency.
Is this groundbreaking stuff or what?  The obese are drowning in excess energy substrates but have low physical endurance?  Umm ... sedentary folks of all weights tend to have low physical endurance.  Use it or lose it.  Obesity imparts physical impediments for mobility to begin with, and requires more energy to be mobile.  In the cause and effect chicken and egg debate, this pre-existing mitochondrial dysfunction angle is the least tenable yet.
The resulting model of obesity is based on a growing body of research demonstrating that altered mitochondrial energy production, particularly in skeletal muscles, is a major anomaly capable of setting off a chain of metabolic events leading to obesity.
Or the chronic energy surplus leads to obesity and sets off a chain of dysfunctional metabolic events.  This whole angle inadvertently just broke off that last tine of TWICHOO.  This notion that the obese have their fat locked away and inaccessible to the cells for burning is diametrically opposed by the observation that the obese have a dramatically lower RQ indicating greater fat burning.  

Remember beepers?  My hubby and I were once out on a lake in a boat and he had his in his swim trunk pocket.  He forgot about that as we dove in the water to refresh.  The beeper initially floated out of his pocket to the surface.  It then started going off as it sunk to the bottom of the lake.  We could hear the BEEP BEep Bweeerp bwwweeeeeerrrrrrrp as it went down.  This is how I see TWICHOO sinking ... and yet some keep diving down after that beeper thinking it may still work.


Duffy Pratt said…
I fell into my pool once with my cell phone in my pocket. I tried to return it, but customer service had seen drowned phones before, and called my bluff. Instead they sold me a new phone at (gasp!) full price. Two days later, for kicks, I tried the dead phone, and it sprang back to life. Electronics are stranger than theories.

And by the way, I will try any form of dieting so long as it allows me to have unlimited quantities of lemon squares and pumpkin cheesecake.
CarbSane said…
My hubby dropped his in the toilet once (luckily before he used it!) If you get the battery out/power down quickly enough and it dries out, it will work again. Yep, they have moisture indicators in them thar phones so they know if it got wet ;) The likelihood of saving drowned electronics is rather slim w/o rapid intervention.
Tonus said…
Fascinating stuff. I admit it feels frustrating when you think you've found a formula that works for better physical health and someone (say, some snarky blogger!) finds research that pushes you back towards square one.

But as they say, life isn't fair and you need to adapt or die. If the formula requires some tweaking and a bit more effort than we anticipated, then we need to refocus and get to work. The alternative is to give up. Some people do that by reverting to previous habits because they feel it's no use to try. Others stick to their current course and ignore any evidence or logic that might require them to change. They stay on track with their diet, but they've given up on improving their health or appearance.

I can understand the desire to debunk ELMM and find a way to eat mindlessly and ignore exercise and still reach ideal health and appearance. But ELMM has proven to be remarkably resilient, hasn't it?