He wrote a fabulous blog on October 12, 2011 and I hope everyone reads it. I'd love to hear what you all think. I know Travis Culp commented in the blog about Mg deficiency and I totally agree with him there is a huge tie there because of the Mg/ATPase. I think Peter is coming around to the fact the the problem is at the mitochondrial level of neurons in the hypothalamus. He used a few paragraphs to convey major points in why we really get fat.
I think this post could replace Gary Taubes GCBC as to why we really get fat. He is knocking on the door in my view here.
The dysfunctional mitochondria notion is enticing, but blown out of the water by the works of Holoszy's group, for example: http://www.pnas.org/content/105/22/7815.full.pdf
My blog post on that study: http://carbsanity.blogspot.com/2011/09/mitochondria-and-high-fat-diets.html
From the paper: It is surprising that the mitochondrial deficiency causes insulin resistance concept has been so widely accepted, because it seems untenable in the context of what is known regarding the capacity of skeletal muscle for oxidative metabolism. The mechanism by which a 30% decrease in muscle mitochondria has been proposed to cause muscle insulin resistance is an impairment in the ability to oxidize fat, resulting in accumulation of intramyocellular lipids (1, 2). 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 (39). The energy/substrate requirement of resting muscle cells is determined by ‘‘housekeeping’’ functions, such as maintenance of transmembrane potential by the Na/K ATPase, protein synthesis, etc., and is very low relative to the maximal capacity of muscle for substrate oxidation. Increasing the supply of FFA or glucose to resting muscle can change the relative proportions of these substrates that are oxidized but does not result in an increase in substrate oxidation above that required to supply the energy needed for ATP repletion, regardless of its content of mitochondria.
As regards Peter's contention: "Fatty acid uptake is (predominantly) controlled at the mitochondrial surface." Actually FA's pass two membranes to be oxidized. Uptake into the cell from circulation and uptake across the mitochondrial membrane once inside the cell. Different mechanisms are involved in each. So, I'm not sure where he gets this definitive statement from.
The adipocyte balloon? A left-over of the part of Taubes' misinformation on the progression of insulin resistance. The overwhelming scientific evidence is that systemic, pathological insulin resistance begins in the fat tissue.
The "Rogge hypothesis" (http://brn.sagepub.com/content/10/4/356.full.pdf) does not meet the initial test of explaining the epidemic of obesity. She implies that some underlying mitochondrial defect results in excess glucose metabolism at the expense of fatty acid oxidation and this is alleviated by increasing intake to increase fat stores. So that when obese folks re-establish a "normal" RQ. Only they don't ... the obese are better fat burners according to their very low RQ. Dysfunctional mitochondria? In the Ranneries study where the formerly obese had a higher resting RQ, the RQ during activity was indistinguishable between groups (http://carbsanity.blogspot.com/2011/10/fat-metabolism-in-formerly-obese-women_06.html). Rogge's cites conflict with Ranneries' results. From the Rogge paper:
In a study of the effects of dietary-induced weight loss in obese adults, weight loss did not alter the overall percentage of energy derived from fat (47%) under resting conditions, but the amount of energy derived from fat in the 5-hr postmeal period was severely depressed. At baseline, obese participants derived 38% of total energy expenditure from fat during the postmeal period; following weight loss, the participants obtained only 26% of their total energy from fat oxidation (Ballor, Harvey-Berino, Ades, Cryan, & Calles-Escandon, 1996). These results are in agreement with the findings of a study comparing the resting and postprandial energy expenditure and substrate use for reduced-obese, weight-stable women and never-obese women (Raben et al., 1994). The two groups of women had no significant differences in their resting energy expenditure or in their use of energy substrates. However, the formerly obese women exhibited a reduction in fat oxidation twice as great as that of the never-obese women following a high-fat meal. In addition, the rate of carbohydrate oxidation was significantly higher among the formerly obese women.
So? The FO burned more carb and less fat. They didn't burn a different amount of total energy. It's ultimately about energy balance. You need the ATP you need. Your body can get it from glucose, fatty acids, amino acids and ketones. This whole mitochondrial dysfunction tangent is getting folks nowhere. But I suppose it is a good face-saving diversion for those who believed Peter when he kept insisting that fasting insulin levels determine weight loss.
This does not concern the science contained in the post in question. I thought I would add a point about the Hyperlipid blog.
I have read Peter's blog on occasion for several years now as he often has an interesting perspective on things.
He is however a good writer and has a certain way with words and the use of rhetoric. I personally find that for people with these skills reading their work requires a certain level of caution. I expect that Peter could go along way to convincing you that veganism is the only longical way forward if he seriously put his mind to it :P Such written work requires more than the usual awareness when reading.
When his arguments coincide with your own personal biases they can be utterly convincing :)
This is a general point and not particularly relating to his current topic of mitochondrial dysfunction.
It's difficult to pin down that initial cause of mitochondrial dysfunction in the pre-obese. As stated, I tend to lean toward a nutrient deficiency, but the implication by Peter seems to be that eating outside of a ketogenic diet could cause it and then "returning" to our default VLC diet brings things back in line. I'd have to see a lot more proof of that. While I have no doubt that ketogenic diets are effective in treating the symptoms of obesity, diabetes, epilepsy etc., I don't view the lack of them as being a primary component in their etiology.
Employing a ketogenic diet is something like taking a drug to treat the symptom. It may be effective and bring about the desired result, but it requires the continued use of it in order to remain "normal." Ketogenic diets are probably almost always safer than pharmaceuticals, but I think most humans in a truly healthy state should be able to eat high carb if they wish with no ill-effects.
I've been reading Peter for years and am quite fond of his hepatic injury role in obesity. But while I understand that he's sticking to the CIH theory, I'm not sure why he's so dismissive of Stephan's theories re food reward:
Oops. Did you just pop the set point hypothesis of obesity? Clumsy of you, but easily done.
Obesity as a function of damaged mitochondria is a compelling theory, but I'm reluctant to let hyper-palatable industrial food off the hook.
So in regard to the RQ in 'normal' people, I looked at the review study where the graph is from but have not yet gone farther back to the referenced studies.
I have taken a metabolic efficiency test twice, and the RQ was far different. I don't think an RQ of .85 would be normal for people on a low carb paleo diet. My RQ during exercise stayed between .58 and .75. This could be an error but I had done the test a year before at the same place and on the same machine and it came back as more 'typical' values.
Do normal RQ values need to be adjusted for people/athletes eating low carb paleo?
Paleo for pets? 27 Answers