9

votes

What did you think about hyperlipid's recent blog post on the adipocyte set point balloon getting popped?

Answered on September 12, 2014
Created October 16, 2011 at 1:38 AM

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.

Hyperlipid: The Adipostat Ballooon.

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 02:08 PM

@Quilt - I don't know why wouldn't I devote time arguing Evelyn. That should be a point of all researchers, to look deeply at conflicting evidence. The best way to prove your theory is to work against it.

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 02:06 PM

Maybe you americans are close minded then :P j/k don't be so dramatic

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 02:06 PM

Matthew, you forgot its all about context, again :P

24df4e0d0e7ce98963d4641fae1a60e5

on October 22, 2011
at 12:39 PM

Oh please maj ... Pointing out that I'm not a dude is close mindedness to you? I don't know what kind of hoods you're riding city busses in, but I've never heard that one on the NYC subways.

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 10:49 AM

Eveyln, why do you think that if you are a chick, you can't be a dude ? This is exactly type of close mind I am talking about :P I got this from young girls while in the city buss - they say something like "where are you sister bro"

2b2c2e4aa87e9aa4c99cae48e980f70d

(1059)

on October 19, 2011
at 02:34 PM

So, Dr. K, no damage from carbs alone, just from the combination of carbs+PUFAs? What about fructose carbs alone?

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:47 AM

Sorry, I tend to dismiss theories for which I've yet to see support. It's a fool's errand to keep looking for that one study to support a theory one is wedded to, but this is exactly what Peter is doing and he is surprisingly open about that as well. Better to let go of the flawed hypothesis, no?

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:43 AM

@Quilt I don't know what dogma you're talking about, or what revolution in biology you're talking about over on Peter's blog. Among your list of articles that you posted for Jane there was this one: http://medind.nic.in/iaf/t09/i4/iaft09i4p324.pdf . On p. 135 top left is a nice graphic demonstrating how the elevated FFA from obesity/chronic energy surplus precipitates the cascade. Nice find!

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:39 AM

Travis, I should have worded that better. The postprandial clearance of dietary fat is an emerging focus of health/disease, specifically the effective trapping of fatty acids by adipocytes. This is impaired in the obese in addition to the usual clamping down of NEFA release. In healthy adults dietary fat is cleared rapidly along with dietary glucose. Following a mixed meal this would mean burning a higher percent glucose and lower percent fat with fat being "buffered" in the adipose tissue. WRT mito dysfunction, it seems more the result not the cause of obesity.

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:30 AM

Hi Travis, A huge area of interest is in the postprandial response. I should perhaps have worded that differently in that *after a meal* we probably want less oxidation of dietary fat and rapid clearance into the fat cells. Yes Jack, the damage is the result not the cause. I don't know what dogma I'm supposed to be arguing. I did a little reading you posted to Jane over at Peter's, and http://medind.nic.in/iaf/t09/i4/iaft09i4p324.pdf is a good one. On p. 335 top left is a nice graphic tracing the issue back to the elevated NEFA in obesity resulting from chronic energy surplus.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 08:15 PM

Travis i think the mitochondria actually can become more efficient again when the cellular terroir also improves with time. Mitochondrial signaling is tied to every known biochemical pathway. I think dysfunction is felt here with chronicity of assaults. I think when you eliminate some combinations of these things the mitochondria are capable of adapting back to normalcy

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 17, 2011
at 08:12 PM

Carbs plus pufas includes carbs does it not? I am confused. :S

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 08:11 PM

Im amazed you guys are wasting time here. She is and has been arguing dogma for quite sometime. Some of us know thatnthis arguement has zero to do with macronutirents but have a lot to do with the multiple assaults the cellular machinery gets from the many things we are not designed to eat in excess.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 08:05 PM

Carbs plus pufas = carbs in your head not mine. The mix is pretty damaging to mitochondria

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 17, 2011
at 08:00 PM

Quilt: "Im not sure that anyone has said carbs damage mitochondria"...one day before > "hypothalamic mitochondria get smoked by pufas and carbs" Cliff how can you possibly counter such a consistent argument!

Medium avatar

(39831)

on October 17, 2011
at 06:09 PM

Carbsane: What do you mean we want to burn less fat as a %? Are you saying the pre/post-obese are healthier than the non-obese in that regard? Also, fatty acid uptake is rate-limited by CPT1 in the mitochondrial outer membrane, so I don't see anything wrong with Peter's statement. Perhaps mitochondrial dysfunction comes down to a problem in carnitine supply or in some mineral that is involved in the proper expression of that enzyme.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 02:43 PM

@maj: For starters, try chick! LOL *I'm* not the one claiming a zillion studies and a lot more evidence on the other side. You're pulling a Quilt here ... What's next? Send me to any biochem text? When someone makes a statement they should be able to back it up, no? Bring it! ;-)

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 02:39 PM

And your point is????

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:10 PM

And please refrain from sentences that *nothing supports his theory*. This is irresponsible from you. One thing is not to agree, another is to dismiss.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:09 PM

It might not explain it but it can sure describe how to act about it. The insulin might not have did it but it sure as hell becomes involved later. I dont trust anybody btw. :P

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:07 PM

I dont trust anybody CS. :P

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:05 PM

BUT, perhaps the fact that we have so many ways for FFA to enter the cell and there is that geometry + transport problem with mitos is a clue. Don't get me wrong, I like the fact that you are opposing, but so far I don't see your evidence compelling - there is **a lot more** evidence on the other side. Ofc you can dig up anything.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:04 PM

BUT, perhaps the fact that we have some many ways for FFA to enter the cell and there is that geometry + transport problem with mitos is a clue.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:03 PM

Carbsane dude, I don't have time to list here zillion of studes, are you insane ? I just lost an hour compiling some vitamin C reference for n00bs. I am sure you know how to use Google Scholar.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:01 PM

I totally agree. You seem to have great view of how physiology works. Ketogenic diet is curative for sure. Malnutrition is the probable reason for obesity. On the other hand, its big unknown how ketogenic diet works on longer or full life time and could it extend life as promoted by Rosedale. If we are talking about what is natural, I guess some carbs are OK, but if we are talking about body hacking, it might be different.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 01:49 PM

OK ... so poor choice of words. I'm aware of the mechanisms by which FFA's get into cells. Glad to know you are as well. I'll await just a half dozen studies ... or perhaps even one ... that support "Fatty acid uptake is (predominantly) controlled at the mitochondrial surface." If he's talking uptake into mitochondria specifically he should have been more clear. It seems that he's talking uptake by the cells to use for energy.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:59 PM

Yes, not lucky use of words with LDL but at the end, you get FFA inside the cell which is what matters.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:57 PM

Appart from that FFA can enter cells via several different mechanisms b) via simple diffusion c)via CD36 receptor d)FFAR receptors

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:56 PM

WIKI FTW: In peripheral tissues, lipoprotein lipase digests part of the VLDL into LDL and free fatty acids, which are taken up for metabolism. This is done by the removal of the triglycerides contained in the VLDL. What is left of the VLDL absorbs cholesterol from other circulating lipoproteins, becoming LDLs. LDL is absorbed via LDL receptors. This provides a mechanism for absorption of LDL into the cell, and for its conversion into free fatty acids, cholesterol, and other components of LDL

E5c7f14800c5992831f5c70fa746dc5c

(12857)

on October 17, 2011
at 12:20 PM

"my central leptin series lays out why the hypothalamic mitochondria get smoked by pufas and carbs" This is what you said....

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 11:34 AM

@majkinetor: If you want to believe that Peter's right about fasting insulin despite the fact that nothing supports this theory, I doubt anything I say will change your mind. He's wrong, provably so on the insulin thing. The damaged mitos causing obesity is as well. It cannot explain the *epidemic*. I'll take the writings of Bierman, McGarry and Frayn on the role of adipocytes in IR over Peter's theories.

7dc950fc76a046048e683d2a27dced37

on October 17, 2011
at 10:59 AM

Dr K, I'm not getting the connection between many people not tolerating the PHD and tolerating implying the ability to eat all macros at times (PHD is moderately low-carb and low in PUFA and fructose).

7dc950fc76a046048e683d2a27dced37

on October 17, 2011
at 10:57 AM

maj, for me, both reward and metabolic dysfunction are factors; which is dominant may be like the "which came first, the chicken or the egg" discussion.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 10:27 AM

@Maj: You can do better than "zillion studies". What do you mean by FFA's enter cell by LDL? If the mitos were dysfunctional, then, for example in Ranneries, the FO would not be able to function virtually identically to the never obese when exercising.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 10:23 AM

@Travis: I assume you're referring to Rogge quote. Obese derived 38% from fat, FO 26%. It's an awful stretch, don't you think, to blame burning more carb vs. fat for causing obesity? We probably want to burn less dietary fat as a percent, efficient clearance of dietary fat into adipose tissue is the healthy metabolic response. One can imagine that deflated adipocytes are better on the take-up, but in other studies, NEFA are still elevated, so the FO adipocytes are still "giving it up" as well ==> no net accumulation unless Ein>Eout. So as you say, the pathway is through overeating.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 08:16 AM

Mito damage might start with PPAR gama dysfunction.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:53 AM

It may be genetics - PPAR gama dysfunction: http://goo.gl/nbC26. This one seem to induce leptin overxpression despite fat cell size which might lead to leptin resistance and obesity.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:50 AM

also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs and/or other mito dysfunction cause infertility goes along with Peter observations. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See http://goo.gl/I6WX

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:50 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs and/or other mito dysfunction cause infertility goes along with Peter observations. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See goo.gl/I6WX For more Paleo hacks: http:

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:49 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs cause infertility goes along with Peter observations: http://goo.gl/hd0Uc (she wrongly concluded that the problem is fat from diet tho) That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See http://goo.gl/I6WX

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:43 AM

Great answer quilt. Some people here live in virtual worlds.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:40 AM

I believe that there might be a factor in reward, but not the dominant one. THC is perfect example. It makes you binge ASAP. Its even used in pregnancy to prevent anorexia and nausea with HG syndrome (THC crosses placenta but its not toxic).

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:37 AM

Carbsane, its also worth noting that the real reason why you stopped taking him seriously might have to do with his aggressive ad hominem attacks toward you and your physiology understanding in one of his posts. While I don't appreciate such outcomes, I find highly improbable that you would skip over that and just despite of it, consider he is actually right.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:36 AM

Carbsane, its also worth noting that the real reason why you stopped taking him seriously might have to do with his aggressive ad hominem attacks toward you and your physiology understanding in one of his posts.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:35 AM

Carbsane, its also worth nothing that Petro that the real reason why you stopped taking him seriously might have to do with his ad hominem attacks toward you and your physiology understanding in one of his posts.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:31 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs cause infertility goes along with Peter observations: http://www.sciencedaily.com/releases/2007/08/070823182738.htm. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See Surface-area-to-volume ratio at http://goo.gl/I6WX1

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:26 AM

Great response Travis. Carbasane is again cherry picking. The rate of mito oxidation doesn't depend only on rate of ATP/ADP. Apart from cells energy need, the other factors inlude tyroid status, redox state, swelling, coenzime availability (i.e. ubiquinol etc). Further, FFA enter cell by LDL which is not limiting factor, and enter mito via carnitine palmitoyl transferase system which IS limiting factor. He gets the 'definite' statement from zillion of studies you can find around, instead of cherry picking one with opposite conclusion.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 02:58 AM

tolerate implies the ability to eat all macronutients at times to survive. Omnivore. The problem we have today is we are not eating real food and that food is filled with two specific macronutrients that cause humans problems when it is present 24/7. (PUFA and Fructose)

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 02:52 AM

Im not sure that anyone has said carbs damage mitochondria. I think cliff and Evelyn heard that in their heads when they read this. I think this clearly shows a bias in perception. Mitochondria are final arbiters of electrons from food. I dont think it matters what macronutrients they come from. I think what does matter is how those electrons are accounted for by the brain. Those 20 trillion cells are controlled by the brains pharmacy, the pituitary. The response is measured by our hormones status.

Medium avatar

(39831)

on October 17, 2011
at 02:36 AM

That's a pretty large reduction in postprandial lipid oxidation in the formerly obese. That would make a big difference over time if they are needlessly oxidizing glucose and thus interfering with glycogenesis. They would then become hungry sooner and consume more energy as a whole as the hypothalamus tries to secure more glucose for the brain. Because most people would be eating mixed meals, fat would come with the glucose and be partitioned in adipocytes. I could see this leading to obesity.

24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 11:07 PM

I think Quilt should have to donate a dollar for every time he fails to capitalize a proper name or use an apostrophe in the word "can't". Sheesh!! According to Peter, the obese have wonderful mitochondria!! It's losing weight that causes formerly obese to become somehow mito-impaired.

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:38 PM

Jay, it is just the constant assumption that no one else before has ever thought that context is important that can be a little trying :P

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:34 PM

Quilt, the word "tolerate" implies that the diet is inherently negative and that some people are merely coping with the diet without showing its ill effects.

3846a3b61bc9051e4baebdef62e58c52

(18635)

on October 16, 2011
at 09:27 PM

"Context" is EVERYTHING when your beyond theory and looking for implementation.

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:19 PM

I think perhaps Quilty should have to donate a couple of dollars to charity for every use of the word "context" :)

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 09:08 PM

I think RQ should be gotten in most people to see how it evolves as they make changes. It does change with time. Some of the really obese in the AMGEN trials never got it back. I think in the woo is one of them......but I bet she just did not allow enough time to reclaim her mitochondrial functioning.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 09:06 PM

Lots of people can tolerate Pauls diet and his recs. MAny cant. This post is about those who cant and why they cant. Taking it a step further can the formerly obese reclaim their mitochondria and RQ......yep. Again, its about those who cant. That is the context of why his post is important.

7dc950fc76a046048e683d2a27dced37

on October 16, 2011
at 02:43 PM

One more thing ... lots of PHD dieters are noticing* what I'm noticing: that following a diet lower in industrial foods/NADs reduces cravings. How does neuronal mitchondrial dysfunction explain this phenomenon? * http://perfecthealthdiet.com/?page_id=4860

7dc950fc76a046048e683d2a27dced37

on October 16, 2011
at 02:27 PM

From my perspective, there is a mechanism that contributes to overeating (J Stanton's series on hunger and wanting vs liking comes to mind on this) that has an evolutionary basis ... the idea that food drives can cause us to override normal appetite mechanisms. This is protective if you're Grok, not so protective if you're the typical stressed Westerner eating fast food. How does Peter's theory tie into this?

24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 02:21 PM

Jeez Quilt, Peter's blown up nothing. I stopped taking him seriously when he blatantly fudged data and nobody on his blog even questioned it. http://carbsanity.blogspot.com/2011/09/bloggo-science-hypothetical-post-iii.html (the post that led to KGH and my mutually buried hatchet).

E5c7f14800c5992831f5c70fa746dc5c

(12857)

on October 16, 2011
at 02:05 PM

carbsane to the rescue!

24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 01:59 PM

Cliff is right, carbs do not damage mitochondria.

E5c7f14800c5992831f5c70fa746dc5c

(12857)

on October 16, 2011
at 01:21 PM

No one has yet to demonstrate how carbs damage mitochondria in healthy people. Its pretty obvious that there is some catalyst in industrial food...

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 12:26 PM

Stabby my mitochondrial series from back in june goes into excruciating detail of why his post makes biologic sense. Moreover, my central leptin series lays out why the hypothalamic mitochondria get smoked by pufas and carbs but not protein.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 12:24 PM

Simple beth.....they dont make sense at the 30000 ft view. Reward tracts are output only tracts. They do nothing to control the metabolic machinery that counts electrons from food. Peter blew that up with a simple post.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 12:21 PM

Its probably the most crucial blog post of 2011 in my view.

98bf2ca7f8778c79cd3f6c962011cfdc

(24286)

on October 16, 2011
at 06:04 AM

My money's on Peter.

Be1dbd31e4a3fccd4394494aa5db256d

(17969)

on October 16, 2011
at 05:00 AM

I think you kind of hinted at it already, but why do the mitochondria get damaged in the first place? Isn't that a leptin resistance problem, which is essentially a crappy neo-neolithic lifestyle problem?

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 02:39 AM

He basically showed that mitochondrial disruption is at the seat of many factors including obesity. It basically blew a hole in some bloggers theories on obesity. It is sciency but I think it is worth your time. It was a great simple little post.

3846a3b61bc9051e4baebdef62e58c52

(18635)

on October 16, 2011
at 02:35 AM

I like that lucky...and I liked his post although its been many years since biochem, or neurophys and I'm very much a bottom line type of guy anymore. Enjoyed the comments too.

66e6b190e62fb3bcf42d4c60801c7bf6

(12407)

on October 16, 2011
at 02:30 AM

more theorizing than anything but i do think he is hitting on an important point. when i tell people the best strategy for the obese to lose weight, i immediately will tell them to get into ketosis and stay there as long as possible. (after a month or so, if possible strength train a couple times a week and eat starch pwo to keep insulin sensitivity but other than that stay in ketosis). i think that this may put forth a mechanism the healing that occurs on at the mitochondrial level that i didn't understand. i do think that testing out starches cyclically is a good idea but it's individual.

Aebee51dc2b93b209980a89fa4a70c1e

(1982)

on October 16, 2011
at 02:02 AM

I don't imagine a non-scientist can make much sense of the Hyperlipid posting. Can someone translate into English? Is he making any specific recommendations for the obese, or is this just theorizing?

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8 Answers

7
24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 01:56 PM

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.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:31 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs cause infertility goes along with Peter observations: http://www.sciencedaily.com/releases/2007/08/070823182738.htm. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See Surface-area-to-volume ratio at http://goo.gl/I6WX1

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:56 PM

WIKI FTW: In peripheral tissues, lipoprotein lipase digests part of the VLDL into LDL and free fatty acids, which are taken up for metabolism. This is done by the removal of the triglycerides contained in the VLDL. What is left of the VLDL absorbs cholesterol from other circulating lipoproteins, becoming LDLs. LDL is absorbed via LDL receptors. This provides a mechanism for absorption of LDL into the cell, and for its conversion into free fatty acids, cholesterol, and other components of LDL

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 02:43 PM

@maj: For starters, try chick! LOL *I'm* not the one claiming a zillion studies and a lot more evidence on the other side. You're pulling a Quilt here ... What's next? Send me to any biochem text? When someone makes a statement they should be able to back it up, no? Bring it! ;-)

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:26 AM

Great response Travis. Carbasane is again cherry picking. The rate of mito oxidation doesn't depend only on rate of ATP/ADP. Apart from cells energy need, the other factors inlude tyroid status, redox state, swelling, coenzime availability (i.e. ubiquinol etc). Further, FFA enter cell by LDL which is not limiting factor, and enter mito via carnitine palmitoyl transferase system which IS limiting factor. He gets the 'definite' statement from zillion of studies you can find around, instead of cherry picking one with opposite conclusion.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:53 AM

It may be genetics - PPAR gama dysfunction: http://goo.gl/nbC26. This one seem to induce leptin overxpression despite fat cell size which might lead to leptin resistance and obesity.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:50 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs and/or other mito dysfunction cause infertility goes along with Peter observations. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See goo.gl/I6WX For more Paleo hacks: http:

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:04 PM

BUT, perhaps the fact that we have some many ways for FFA to enter the cell and there is that geometry + transport problem with mitos is a clue.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 10:23 AM

@Travis: I assume you're referring to Rogge quote. Obese derived 38% from fat, FO 26%. It's an awful stretch, don't you think, to blame burning more carb vs. fat for causing obesity? We probably want to burn less dietary fat as a percent, efficient clearance of dietary fat into adipose tissue is the healthy metabolic response. One can imagine that deflated adipocytes are better on the take-up, but in other studies, NEFA are still elevated, so the FO adipocytes are still "giving it up" as well ==> no net accumulation unless Ein>Eout. So as you say, the pathway is through overeating.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:05 PM

BUT, perhaps the fact that we have so many ways for FFA to enter the cell and there is that geometry + transport problem with mitos is a clue. Don't get me wrong, I like the fact that you are opposing, but so far I don't see your evidence compelling - there is **a lot more** evidence on the other side. Ofc you can dig up anything.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 01:49 PM

OK ... so poor choice of words. I'm aware of the mechanisms by which FFA's get into cells. Glad to know you are as well. I'll await just a half dozen studies ... or perhaps even one ... that support "Fatty acid uptake is (predominantly) controlled at the mitochondrial surface." If he's talking uptake into mitochondria specifically he should have been more clear. It seems that he's talking uptake by the cells to use for energy.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:50 AM

also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs and/or other mito dysfunction cause infertility goes along with Peter observations. That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See http://goo.gl/I6WX

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:30 AM

Hi Travis, A huge area of interest is in the postprandial response. I should perhaps have worded that differently in that *after a meal* we probably want less oxidation of dietary fat and rapid clearance into the fat cells. Yes Jack, the damage is the result not the cause. I don't know what dogma I'm supposed to be arguing. I did a little reading you posted to Jane over at Peter's, and http://medind.nic.in/iaf/t09/i4/iaft09i4p324.pdf is a good one. On p. 335 top left is a nice graphic tracing the issue back to the elevated NEFA in obesity resulting from chronic energy surplus.

E5c7f14800c5992831f5c70fa746dc5c

(12857)

on October 16, 2011
at 02:05 PM

carbsane to the rescue!

Medium avatar

(39831)

on October 17, 2011
at 02:36 AM

That's a pretty large reduction in postprandial lipid oxidation in the formerly obese. That would make a big difference over time if they are needlessly oxidizing glucose and thus interfering with glycogenesis. They would then become hungry sooner and consume more energy as a whole as the hypothalamus tries to secure more glucose for the brain. Because most people would be eating mixed meals, fat would come with the glucose and be partitioned in adipocytes. I could see this leading to obesity.

Medium avatar

(39831)

on October 17, 2011
at 06:09 PM

Carbsane: What do you mean we want to burn less fat as a %? Are you saying the pre/post-obese are healthier than the non-obese in that regard? Also, fatty acid uptake is rate-limited by CPT1 in the mitochondrial outer membrane, so I don't see anything wrong with Peter's statement. Perhaps mitochondrial dysfunction comes down to a problem in carnitine supply or in some mineral that is involved in the proper expression of that enzyme.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 08:11 PM

Im amazed you guys are wasting time here. She is and has been arguing dogma for quite sometime. Some of us know thatnthis arguement has zero to do with macronutirents but have a lot to do with the multiple assaults the cellular machinery gets from the many things we are not designed to eat in excess.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:59 PM

Yes, not lucky use of words with LDL but at the end, you get FFA inside the cell which is what matters.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 08:16 AM

Mito damage might start with PPAR gama dysfunction.

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 10:27 AM

@Maj: You can do better than "zillion studies". What do you mean by FFA's enter cell by LDL? If the mitos were dysfunctional, then, for example in Ranneries, the FO would not be able to function virtually identically to the never obese when exercising.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 12:57 PM

Appart from that FFA can enter cells via several different mechanisms b) via simple diffusion c)via CD36 receptor d)FFAR receptors

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:49 AM

I also find intriguing that replacing infertile woman mitochondria with those of healthy young woman will make them far easier to conceive. This is reproduced and confirmed in number of studies. That fat eggs cause infertility goes along with Peter observations: http://goo.gl/hd0Uc (she wrongly concluded that the problem is fat from diet tho) That swelling is is indeed factor in utilization is well known phenomena - its pure mathematics and larger cells are slower and can't keep up, thats why bacteria can't grow larger - they are kept in check by geometry. See http://goo.gl/I6WX

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:03 PM

Carbsane dude, I don't have time to list here zillion of studes, are you insane ? I just lost an hour compiling some vitamin C reference for n00bs. I am sure you know how to use Google Scholar.

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:43 AM

@Quilt I don't know what dogma you're talking about, or what revolution in biology you're talking about over on Peter's blog. Among your list of articles that you posted for Jane there was this one: http://medind.nic.in/iaf/t09/i4/iaft09i4p324.pdf . On p. 135 top left is a nice graphic demonstrating how the elevated FFA from obesity/chronic energy surplus precipitates the cascade. Nice find!

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:39 AM

Travis, I should have worded that better. The postprandial clearance of dietary fat is an emerging focus of health/disease, specifically the effective trapping of fatty acids by adipocytes. This is impaired in the obese in addition to the usual clamping down of NEFA release. In healthy adults dietary fat is cleared rapidly along with dietary glucose. Following a mixed meal this would mean burning a higher percent glucose and lower percent fat with fat being "buffered" in the adipose tissue. WRT mito dysfunction, it seems more the result not the cause of obesity.

24df4e0d0e7ce98963d4641fae1a60e5

on October 22, 2011
at 12:39 PM

Oh please maj ... Pointing out that I'm not a dude is close mindedness to you? I don't know what kind of hoods you're riding city busses in, but I've never heard that one on the NYC subways.

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 10:49 AM

Eveyln, why do you think that if you are a chick, you can't be a dude ? This is exactly type of close mind I am talking about :P I got this from young girls while in the city buss - they say something like "where are you sister bro"

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 02:08 PM

@Quilt - I don't know why wouldn't I devote time arguing Evelyn. That should be a point of all researchers, to look deeply at conflicting evidence. The best way to prove your theory is to work against it.

77877f762c40637911396daa19b53094

(78467)

on October 22, 2011
at 02:06 PM

Maybe you americans are close minded then :P j/k don't be so dramatic

6
0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 06:20 PM

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.

4
7dc950fc76a046048e683d2a27dced37

on October 16, 2011
at 11:43 AM

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.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:40 AM

I believe that there might be a factor in reward, but not the dominant one. THC is perfect example. It makes you binge ASAP. Its even used in pregnancy to prevent anorexia and nausea with HG syndrome (THC crosses placenta but its not toxic).

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 09:06 PM

Lots of people can tolerate Pauls diet and his recs. MAny cant. This post is about those who cant and why they cant. Taking it a step further can the formerly obese reclaim their mitochondria and RQ......yep. Again, its about those who cant. That is the context of why his post is important.

24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 11:07 PM

I think Quilt should have to donate a dollar for every time he fails to capitalize a proper name or use an apostrophe in the word "can't". Sheesh!! According to Peter, the obese have wonderful mitochondria!! It's losing weight that causes formerly obese to become somehow mito-impaired.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 12:24 PM

Simple beth.....they dont make sense at the 30000 ft view. Reward tracts are output only tracts. They do nothing to control the metabolic machinery that counts electrons from food. Peter blew that up with a simple post.

3846a3b61bc9051e4baebdef62e58c52

(18635)

on October 16, 2011
at 09:27 PM

"Context" is EVERYTHING when your beyond theory and looking for implementation.

7dc950fc76a046048e683d2a27dced37

on October 16, 2011
at 02:43 PM

One more thing ... lots of PHD dieters are noticing* what I'm noticing: that following a diet lower in industrial foods/NADs reduces cravings. How does neuronal mitchondrial dysfunction explain this phenomenon? * http://perfecthealthdiet.com/?page_id=4860

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:35 AM

Carbsane, its also worth nothing that Petro that the real reason why you stopped taking him seriously might have to do with his ad hominem attacks toward you and your physiology understanding in one of his posts.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:09 PM

It might not explain it but it can sure describe how to act about it. The insulin might not have did it but it sure as hell becomes involved later. I dont trust anybody btw. :P

7dc950fc76a046048e683d2a27dced37

on October 17, 2011
at 10:57 AM

maj, for me, both reward and metabolic dysfunction are factors; which is dominant may be like the "which came first, the chicken or the egg" discussion.

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:38 PM

Jay, it is just the constant assumption that no one else before has ever thought that context is important that can be a little trying :P

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:34 PM

Quilt, the word "tolerate" implies that the diet is inherently negative and that some people are merely coping with the diet without showing its ill effects.

24df4e0d0e7ce98963d4641fae1a60e5

on October 16, 2011
at 02:21 PM

Jeez Quilt, Peter's blown up nothing. I stopped taking him seriously when he blatantly fudged data and nobody on his blog even questioned it. http://carbsanity.blogspot.com/2011/09/bloggo-science-hypothetical-post-iii.html (the post that led to KGH and my mutually buried hatchet).

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:07 PM

I dont trust anybody CS. :P

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:36 AM

Carbsane, its also worth noting that the real reason why you stopped taking him seriously might have to do with his aggressive ad hominem attacks toward you and your physiology understanding in one of his posts.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 07:37 AM

Carbsane, its also worth noting that the real reason why you stopped taking him seriously might have to do with his aggressive ad hominem attacks toward you and your physiology understanding in one of his posts. While I don't appreciate such outcomes, I find highly improbable that you would skip over that and just despite of it, consider he is actually right.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 02:58 AM

tolerate implies the ability to eat all macronutients at times to survive. Omnivore. The problem we have today is we are not eating real food and that food is filled with two specific macronutrients that cause humans problems when it is present 24/7. (PUFA and Fructose)

7dc950fc76a046048e683d2a27dced37

on October 16, 2011
at 02:27 PM

From my perspective, there is a mechanism that contributes to overeating (J Stanton's series on hunger and wanting vs liking comes to mind on this) that has an evolutionary basis ... the idea that food drives can cause us to override normal appetite mechanisms. This is protective if you're Grok, not so protective if you're the typical stressed Westerner eating fast food. How does Peter's theory tie into this?

24df4e0d0e7ce98963d4641fae1a60e5

on October 18, 2011
at 10:47 AM

Sorry, I tend to dismiss theories for which I've yet to see support. It's a fool's errand to keep looking for that one study to support a theory one is wedded to, but this is exactly what Peter is doing and he is surprisingly open about that as well. Better to let go of the flawed hypothesis, no?

0bc6cbb653cdc5e82400f6da920f11eb

(19245)

on October 16, 2011
at 09:19 PM

I think perhaps Quilty should have to donate a couple of dollars to charity for every use of the word "context" :)

7dc950fc76a046048e683d2a27dced37

on October 17, 2011
at 10:59 AM

Dr K, I'm not getting the connection between many people not tolerating the PHD and tolerating implying the ability to eat all macros at times (PHD is moderately low-carb and low in PUFA and fructose).

24df4e0d0e7ce98963d4641fae1a60e5

on October 17, 2011
at 11:34 AM

@majkinetor: If you want to believe that Peter's right about fasting insulin despite the fact that nothing supports this theory, I doubt anything I say will change your mind. He's wrong, provably so on the insulin thing. The damaged mitos causing obesity is as well. It cannot explain the *epidemic*. I'll take the writings of Bierman, McGarry and Frayn on the role of adipocytes in IR over Peter's theories.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:10 PM

And please refrain from sentences that *nothing supports his theory*. This is irresponsible from you. One thing is not to agree, another is to dismiss.

3
Medium avatar

on October 17, 2011
at 02:34 AM

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.

77877f762c40637911396daa19b53094

(78467)

on October 17, 2011
at 02:01 PM

I totally agree. You seem to have great view of how physiology works. Ketogenic diet is curative for sure. Malnutrition is the probable reason for obesity. On the other hand, its big unknown how ketogenic diet works on longer or full life time and could it extend life as promoted by Rosedale. If we are talking about what is natural, I guess some carbs are OK, but if we are talking about body hacking, it might be different.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 17, 2011
at 08:15 PM

Travis i think the mitochondria actually can become more efficient again when the cellular terroir also improves with time. Mitochondrial signaling is tied to every known biochemical pathway. I think dysfunction is felt here with chronicity of assaults. I think when you eliminate some combinations of these things the mitochondria are capable of adapting back to normalcy

3
77877f762c40637911396daa19b53094

(78467)

on October 16, 2011
at 11:09 AM

It looks like mitos are in the root of everything in life and universe.

I will switch my priorities in keeping them happy.

3
1a98a40ba8ffdc5aa28d1324d01c6c9f

(20378)

on October 16, 2011
at 06:29 AM

Very nice and the blog is a great find.

1
64433a05384cd9717c1aa6bf7e98b661

(15236)

on October 16, 2011
at 05:55 PM

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?

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 09:08 PM

I think RQ should be gotten in most people to see how it evolves as they make changes. It does change with time. Some of the really obese in the AMGEN trials never got it back. I think in the woo is one of them......but I bet she just did not allow enough time to reclaim her mitochondrial functioning.

1
64433a05384cd9717c1aa6bf7e98b661

(15236)

on October 16, 2011
at 05:34 AM

Wow seeing the RQ that low in obese people surprised me.

I have to re-read this blog a few times I think.

Ed71ab1c75c6a9bd217a599db0a3e117

(25472)

on October 16, 2011
at 12:21 PM

Its probably the most crucial blog post of 2011 in my view.

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