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Sunday, May 19, 2013

De Novo Lipogenesis Again (and Science and Science Reporting)

In my last post, I just posted a graphic taken from an "FYI" inset by a scientist, Marc Hellerstein, whose work I've blogged on quite a bit here. (Anyone wanting to refresh can click on the image and enlarge.)  One good post to begin with if you are not familiar with that name is Where do Triglycerides Come From? I would say that between Marc Hellerstein's No common energy currency: de novo lipogenesis as the road less traveled and the works of Eric Jequier such as Nutrient effects: post-absorptive interactions, the case that hepatic DNL is quantitatively insignificant in human energy balance/fat accumulation is strong and has not been refuted by some newer scientific findings.    

I do hope to expand on the role of adipose DNL at some future point -- teaser: I have a paper showing that reducing WAT lipolysis upregulates adipose DNL and improves glucose homeostasis in the IGT irrespective of body weight  -- but adipose DNL had not been central to the arguments of folks from Taubes to Lustig to Eades to Naughton to a list far too long to go through here.  The claim has been that excess carbs are converted in the liver to fat and sent to the fat tissue for storage.  

Does this occur?  Yes.  Is it significant?   Only if you consider a couple grams fat synthesis per day significant at the metabolic cost "wasting" one gram carb for every four grams converted to fat ... and only if you consider a few grams of fat significant in the context of consuming 100, 200 or more grams of fat that is already fat.
So on the last post, Beth of Weight Maven blog made the following comment.  
I must admit to being pretty skeptical of extrapolating the results of overfeeding carbs to normal weight folk. A quick Google search turned up a more recent piece on 60 Minutes from 2012 with one of the researchers in the above piece (Jean Marc Shwarz) telling Sanja Gupta re fructose that "we know that if you look at specific types of fat in the blood there is huge proportion maybe 30% to 40% of that fat in some condition can come from that sugar." Gupta: "So if people say are you sure sugar gets turned into fat, you say yes?" Shwarz: "Here it is ... it becomes very obvious that fructose was a powerful way to stimulate the conversion of sugar to fat."
See cbsnews.com/video/watch/?id=74...
In a frustrating way to start the day, I lost the rather lengthy response to an inadvertent browser refresh, but it's all the same because I decided this would make a better blog post after all.  Unfortunately the video is not in a format I can embed here but here's a screenshot to keep the visual fresh.


There's the powerpoint on the computer, the GC/MS in the background behind Jean-Marc Schwarz in the lab coat and Sanjay Gupta ....  the setup is classic staging for science reporting nowadays.   The caption is somewhat laughable, as mass spectrometry was hardly described as cutting edge roughly 25 years ago when I used it in a former life, and Schwarz (with Hellerstein) has been using this method for roughly 20 years.    Caveats aside, I picked this screenshot for what's on the computer screen:  fructose on the lower left, and palmitate on the lower right. 

Schwarz has been involved in studies designed to elucidate a hypothesized role for fructose in metabolic disorders for a while now, and I'm afraid he's gotten a little caught up in the hyping of it all.   As someone who worked with gas chromatographs in a past life (though usually with an electrochemical detector, not a mass spec) I kinda cringed a little at the description of how they separated the fatty acids in gas in the oven, but ...   In any case, Gupta sets this up as that there was some mystery as to whether fructose could be converted to fat ... as if that were some novel discovery.  The conversion of carbs to fat is discussed on p. 201 of Newsholm & Start's Regulation in Metabolism (1973, thus at least 40 year old biochemistry though I'm sure it's been around much longer I just don't have the time to track down the actual discovery) so it should hardly be a surprise and it's really just scientific journalistic sensationalism that Gupta is engaged in here.   I want to discuss two parts of this discussion.  First:
Gupta:  So after separating out the fatty acids and then analysing it ... you can definitively say that sugar that was tagged like this ... got turned into ... not only did it get turned into fat but it got turned into a very specific kind of fat.
Schwarz:  Right
Gupta:  I find it ... I find that amazing still ... Because I ... I don't ... know ... Did you, did you believe that this was true before you started studying this?
So Dr. Sanjay Gupta who seems by all accounts to be a very accomplished doctor (what happens to these guys/ladies when they hit the media???) is acting like he never heard of this concept before, that this is some novel finding!  I find that disturbing, but this is what journalism has been reduced to.  It's not like he's new to this sort of gig and he sounds -- as a medical doctor -- amazed at the prospect that sugar can be turned to fat in the human body.  Sigh.

Nobody claims that carbs cannot be turned into fat.  Nobody claims they aren't turned into fat.  Where the issue lies is in the degree to which this happens, and more specifically, the degree to which this happens in the liver and subsequently contributes to adipose tissue lipid stores.  The overwhelming evidence points to hepatic DNL being quantitatively insignificant in humans.  The books and videos out there are incorrect, and the technology discussed in this particular 60 minutes piece is hardly new:  Schwarz JM, Neese RA, Basinger A, Hellerstein MK. Effect of oral fructose on lipolysis, fat oxidation, fractional and absolute de novo lipogeneis (DNL) using mass isoptomer distribution analysis (MIDA).FASEB J 1993;7:867(abstr).   Unfortunately I cannot track down that reference cited in this 2001 article:  De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women .  I'll get to this in a moment, but first I want to address the highlighted part of Gupta's comment above.  Because of (a) what that fat is, and (b) how the shocking findings cited by Schwarz are not really all that shocking after all.  So fructose is bad ... really bad ...
Gupta:  ... You're saying fructose is getting turned directly into the, some of the worst kinds of fat in the body.  (Schwarz can be heard saying yes, yeah in the background.)
This presents a clear inconsistency for those arguing that saturated fats are not harmful.  If they are not, then what would be the problem with endogenously produced palmitic acid?   And if they are, there's no comparison between a few grams of carb-derived palmitate compared to the fat bombs so many are proudly downing.   
Schwarz:   We know that if you look at specific fat in the blood,  there is huge proportion, maybe thirty percent to forty percent of that fat in some condition,  can come from that sugar.  And that's, that's a lot in terms of, of a,  of fat in the blood that are associated with health risks.  
If you like what he's saying about fructose here, you have to accept that Schwarz is on the side of saturated fat being bad fat side.  Otherwise that would be called cherry picking.  But Schwarz is not saying anything that conflicts with the Hellerstein inset above.   Note the words I highlighted here.  He is talking about palmitate, which normally comprises around 25% of free fatty acids in the blood so under SOME conditions it would not be totally unfathomable to find 30-40% of the palmitate from DNL.   

Schwarz, despite his statements of scientific satisfaction and surprise and whatnot at the ability for fructose to stimulate DNL, is on the record for almost two decades saying that DNL is not quantitatively significant.   During those same two decades there's no peer review literature that I've come across that even comes close to supporting the wild claims made by Taubes, Lustig, etc.etc.    Furthermore, more reasonable intakes of fructose in energy balance are so inept at producing any sort of reasonable response, almost all DNL experiments involve some sort of overfeeding or large bolus dose.  

To Beth's question as to whether this might be different in the obese, in  this paper (previously linked) , DNL was measured in lean and obese under energy balance (control) and 50% overfeeding of either glucose or fructose.  Here's the results and conclusions:
Results: De novo lipogenesis did not differ significantly between lean and obese subjects, except with the control treatment, for which de novo lipogenesis was greater in the obese subjects. De novo lipogenesis was 2- to 3-fold higher after overfeeding by 50% than after the control treatment in all subjects. The type of carbohydrate overfeeding (sucrose or glucose) had no significant effect on de novo lipogenesis in either subject group. Estimated amounts of absolute VLDL production ranged from a minimum of 2 g/d (control) to a maximum of 10 g/d after overfeeding. This compares with a mean fat balance of ≈275 g after 96 h of overfeeding. Individual subjects showed characteristic amounts of de novo lipogenesis, suggesting constitutive (possibly genetic) differences.

Conclusion: De novo lipogenesis increases after overfeeding with glucose and sucrose to the same extent in lean and obese women but does not contribute greatly to total fat balance.

Might DNL be significant in VLF scenarios?  Possibly.  But that is not relevant in the context of the obesigenic Western diet and why it is so fattening.

Schwarz and Hellerstein are among the authors on a number of fairly recent papers comparing fructose to glucose sweetened beverages.  Whatever these studies show is tainted by the fact that while fructose is present in free form (sometimes quite high concentrations) in nature, it is generally at least partially balanced with free glucose and/or combined with glucose in sucrose in those same foods.  In one study, participants were consuming 150 grams of fructose a day for 10 weeks.   I found some interesting new stuff while trying to track down (unsuccessfully) the Schwarz references 10-12 in the above paper.  Maybe someday when this topic comes up again I can fashion them into a review post of sorts.

In closing, I want to say something about Fun with Statistics.  When presenting data to an audience, it is certainly valid for the presenter to choose whichever accurate means they choose to do so.  It is, however, disheartening to see a scientist do so in the mass media to feed into anti-sugar hysteria.   Let's presume there's this rare deadly disease that I have a 1:50,000 odds of developing, or a 0.002% chance of developing.  And let's stipulate that some study demonstrated that eating the equivalent of 1T sugar per day increased my chances of developing this disease to 1:10,000 or 0.01%.  My chances of getting the disease are 5X as great, or I have a 400% greater chance of developing the disease, etc.  All of which sound nasty compared to the absolute increase in my risk of 0.008 % .

This is a bit more extreme than the way DNL and fructose are portrayed, but not really all that much because we are often talking consumption exceeding even the purported average consumption of your SAD eater.  Couple that with the fact that anything more than low single digit grams of fat are synthesized from carbs and what we have here, folks, is a red herring.  Why Schwarz chose to describe this phenomenon he himself has described as some-variation of inconsequential as mind-blowing is unclear.   It is perhaps an attempt to dumb down metabolism into a visual the masses can latch onto, but I don't think misleading people on the science is ever the way to go.

42 comments:

Sanjeev Sharma said...

being as charitable as I possibly can I see 2 possibilities: maybe Schwartz is "that guy" in his group ... the stubborn one whose opinions have to be weeded out when a paper goes through peer review.

OR Gupta asked him for the worst case scenario and edited out qualifications. Seems hard to see but I've seen even worse hack/hit jobs on reality TV, where the final words came out exactly (pi radians[0]) to the original words.

In many settings the group lead goes out of his way to encourage at least one member to disagree.

[0] 180 degrees

Sanjeev Sharma said...

lots of people like to (seize on)/leverage this as a justification to eat unlimited quantities of carbohydrate.

Combine this with human blind spots, self-deceptions, cognitive biases, memory biases plus the tendency to cheat "just a little bit" and these same people (who are looking for an easy solution to overeating, that's WHY they make this proposal) always eat some fat along with the 4,000 calories of carbohydrate. Then they claim the carbohydrates made them fat.

The ONLY way to use the "very little fat from carbohydrates" to eat massive quantities is to eat an artificial, zero-fat diet; maybe 100% of calories from pure maltodextrin.

and allow absolutely ZERO cheating.

ZERO.

Kade Storm A.K.A. Hedonist said...

I must say that I find it highly challenging for anyone to consume in excess of 3000 calories worth of legumes, tubers, fruits and vegetables. I believe you've talked about this subject from time to time yourself. Not to mention, there's little certainty that all of those calories paired with the water content and fibre bulk would get absorbed anyway.

Sanjeev Sharma said...

I've been "that guy" in a group before and I appreciate how the role's needed in many instances.

I suspect all this has much more to do with TV editing than with Schwarz and Gupta

http://ffffunny.com/images/8703-how-science-reporting-works-

> so busy are you at trashing Schwarz
his published statements are at variance with this interview. What's not to trash?

Sanjeev Sharma said...

It's what my traditional north Indian parents fed me growing up - rice & lentils or lentils & chapatis for most meals.

Fattiest thing we ever ate was skinless boiled chicken.

I got obese on that - growing up it never felt like it filled me up and I just kept eating and eating plate full after plate full.

Kade Storm A.K.A. Hedonist said...

I see. Thanks for the personal anecdote. Sorry to hear about the dietary struggle into obesity.

When I hear accounts like this one, I do wonder if there's a neglected but sizeable sub-population of individuals who're a standing exception to some of these dietary ideas. Who knows, perhaps some of us have poor glucose metabolism--not in the diabetes sense--and tend to have significant levels of DNL and a poor satiety response, compounded further by the energy lost to the DNL process.

George Henderson said...

I don't know where your copy of Good Calories/Bad Calories was printed but I remember a lot of discussion of adipocyte DNL and triglyceride synthesis in mine. Check to see if there are any pages missing.

carbsane said...

Diana, I didn't see anyone trashing Schwarz here, and I don't think it is really appropriate for anyone to contact a scientist to pester them about what they might have said in an interview of this nature.

It's interesting that you mention insulin because Schwarz was involved in this paper: Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-h glucose and insulin excursions

Some names there show up a LOT together in the literature -- I speak of Stanhope and PJ Havel. This is a 2011 paper and I believe the publication count from the same study is at least 3. The other two being: Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women (2012) and Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans (2009)

This study involved establishing maintenance requirements of overweight/obese subjects on a 55% carb, 15% protein, 30% fat diet. They then replaced 25% (around 600 cal on average) with fructose or glucose sweetened beverages, with the remaining 30% carb to come from "complex carbs". What happened, however, is that the subjects did not compensate properly for this and ended up consuming more calories and gaining weight during the 10 week intervention.

I intend to revisit these studies here at some point but I rather prefer to get back to what caught my interest vis a vis diabetes and insulin resistance a while back now. However the "fatal" problem with this study is that they were giving subjects 125g/day glucose or fructose and almost nobody drinks fructose-only sweetened beverages. To drink 125g of sugary beverages that's two 20 oz Cokes which would only contain around 70g fructose along with glucose.



I'm not trying to shill for Coke, as I believe I'm firmly on the record here fingering liquid calories as at least part of the problem in this obesity epidemic. For whatever reason, we are taking in more and more liquid calories and our bodies do not seem to compensate well. This is what happened in this study -- subjects ate somewhat less of solid foods, but did not fully compensate, therefore they consumed more calories and gained weight.

carbsane said...

People are very quick to impugn the integrity of scientists who begin with hypotheses in conflict with their biases or whose work is funded by Big Pharma, etc. This, usually, for what is written in the peer-review literature (and said journal's reputation is important here too). Bloggers calling these scientists stupid, dishonest and worse is all too common.


In this case the disconnect between what is in the peer review and what he said on TV are in pretty stark contrast, and it's his own work and words, not even the research of others with which it might be plausible that he's unfamiliar.


So yeah, I find this troubling and your speculation charitable. Perhaps I'll speculate more in a future comment.

Diana Moon said...

" Where do you perceive the slight, exactly? "

I'm laughing. Do you think an old gal like me is going to fall for this nonsense? Not going to engage. Any objective observer will read what you wrote: an open insult. And the rest of your comments drip with contempt.

"his peer reviewed, edited statements are at variance with this
interview. I thought of it more as guessing where this difference
originated than trashing, but the statements do differ - What's not to
trash?"


His peer reviewed edited statements (26 more than yours) precede the latest 2013 findings. Read that, maybe he's found new things. That's what science is.


But it's nice to see that you admit to trashing him.

Diana Moon said...

Here is a link to an article about Schwarz and his research. Popular, but good:

http://www.tu.edu/news/VTH_Schwarzfructose.html

It's from Touro College, where his lab is, and the PR aspect of this in escapable, but that doesn't sour me on his research.

I find this particularly interesting: "Through his many years of research, he said he's found that ingestion of high fructose corn syrup, particularly after short bursts of overfeeding, leads to rapid development of fat cells."


Particularly after short bursts of overfeeding...that would describe how most Americans get their HFCS: in a large fat/carb/protein meal, in soda. A Bray overfeeding study in real life.


The overfeeding meal is bad enough, but the HFCS dose is like a one-two punch.


Now I'll leave all of you to trash Schwarz. Have fun.

eulerandothers said...

Sanjeev, is a chapati made with oil? I'm not talking about the griddle (a small amount), but something to hold the chapati together...

carbsane said...

I realize this is in response to Sanjeev, but I don't see him trashing Schwarz's science ... he appears to be (and he used the word so I'll not comment either way there) addressing the contradictions between his wealth of peer reviewed science (and I believe the first linked paper in my other comment is one of the better reported studies -- full text is free AND a ton of supplementary material ). They published two papers on that same study in 2011 and 2012. I highly doubt a review paper on epidemiologic and clinical evidence will include anything new.

Radhakrishna Warrier said...

Normally no, but some people (including my wife) add a little (actually very little) oil in the chapatti dough to make the chapatti a softer.


Regards,
Rad

Sanjeev Sharma said...

No added oil(s), saturated or unsaturated anywhere in the chain (stone ground to mouth) as my elders used to make it.

Modern Indians, the ones I've eaten with ... in India, Britain (several generations) and Canada (several generations) ... no oil until they're hot & on the plate, then slather butter ALL OVER. It tastes amazing but it must quadruple the calorie count.

Anthony Singleton said...

Great to see Jimmy looking so happy. He and his Wife have had some very hard knocks over the past few years, but they never stop fighting. Jimmy has shown without a doubt, anyone can get to a safe weight. For some it is easy for others very hard, but the message has to be, you can do it and there are thousands of people willing to help. If you are having trouble losing weight, or controlling your diabetes, don’t give up.

What’s you take on Jimmy’s latest pics Evelyn ?

http://thelowcarbdiabetic.blogspot.co.uk/2013/05/jimmy-moore-has-last-laugh.html

carbsane said...

Since my current copy of GCBC is a Kindle ebook, I doubt anything is missing. He does discuss "lipogenesis" a lot, but that refers to esterification of existing fatty acids to triglycerides.


No that last paragraph mentions overeating. That doesn't happen in Taubes fantasy world ...

carbsane said...

I'm not soured on his research one bit. His peer review literature is quality.

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Screennamerequired said...

I started eating legumes again the other week and was blown away by how satiating they were. I had a small bowl of soup with about 150 calories of red beans and I was so stuffed I didn't feel like dinner.

Sanjeev Sharma said...

OMG poor guy ... his left leg was amputated, and he can still smile that usual charming boyish smile?

damng ... keep on truckin Jimmy.

Sanjeev Sharma said...

> Thanks for the personal anecdote.

Thanks for underlining and bolding the point. I should have put in my usual "memory errors and biases" blurb.

> tend to have significant levels of DNL

I really, really doubt I'm an outlier in this regard - I doubt I'm an exceptional DNL'er

it was the continual small amounts of dietary fat plus continual small amounts of DNL over time.

1-5 grams per day stored is plenty to get one obese in a couple of years.

> and a poor satiety response


heh ... no, not in my case.



I do NOT recall feeling hungry particularly often or feeling extreme hunger ever growing up.



the issue was LOVING the taste (even though by modern standards it might be seen as roughly tasteless, given its low fat and low protein content)



and that issue was exacerbated by LOVING the feeling of eating to fullness.


Had the food been highly palatable and fatty I really can easily imagine myself being hyper obese.

Lighthouse Keeper said...

It would be nice if Mr Moore would make his new book available for free download as did Dr Bert Herring with his Fast - Five I.F. book ( one of his former podcast guests) whilst retaining income from hard cover sales . Many of his fellow countrymen are now in dire straits, some living in cars or R.V.s and not likely to be able to afford it if they are going to have to fork out for grass fed beef, coconut oil etc as well.

carbsane said...

Define significant ... Statistically significant vs. quantitatively/clinically significant are two different things. If one uses 2 g/day normal DNL, then obese pump out 2.2g/day and healthy 2.1g/day with hyperinsulinemia while NAFLD pump out 2.3 to 2.5g/day.

The major DNL product of the liver is palmitate.

Diana Moon said...

Well, my name isn't Evelyn but since you asked this on an open blog,
I'll chime in.

Jimmy looks thinner now than at 306 - duh. But he doesn't
really look good, to me. He looks very wasted and drawn, like someone who is really fighting hard against biology.

Regarding the weight loss itself, let's we wait a year to draw conclusions from this. As Chou En Lai said about the French Revolution, "It's too soon to tell."

Because haven't we been here before? He's lost weight only to gain it - let's
see what happens when the motivation fails.

Also, although I do not read his blog often, I gather that he has been IFing - eating once every 24 hours, or 12 hours.

Anyone can lose weight if they do that consistently. Hell, if I did that, I'd be 100 pounds! The fact that he has done this for a year shows that he must have been pretty damned desperate. When I was desperate, I IFed and felt virtuous. Now that the proximate motivation has vanished, I hate it. Sooner or later, the body rebels.

How lucky and fortunate we all are to be able to choose to turn down food!

carbsane said...

I'm glad you shared your thoughts here. I'm going to address this elsewhere soon because it's really off topic Anthony.


Everyone else, feel free to comment here if you'd like.

H Marks said...

Nutty K/JM update....plz!!

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Diana Moon said...

It was off topic and I had reservations about "feeding the troll" but what the hell. This is not my blog. What you consider in appropriate, including my comments, you can remove.

Anthony, since you've already dragged the discussion off-topic, I've come across research which indicates that very low-carb diets are truly bad for the heart, specifically, it causes or enhances endothelial dysfunction.

http://hyper.ahajournals.org/content/51/2/376.long


(Evelyn, I got this via another blogger but I'm not putting the link here because I'm not sure of the netiquette. Are you supposed to do that? If so I will put it.)


There is more to life than weight loss. Diabetes is quite serious but people have cured their diabetes with very low calorie diets, vegan diets, etc.

The originators of Paleo never intended for their ideas to become vulgarized to line the pockets of people hawking dangerous ideas. Nor did they ever say it was "low carb," just "lower carb" and different carb.

carbsane said...

Linking? As a comment on a blog I'd say just the article is fine unless the blog post you got it from added insight or made comments you are discussing.


No probs with your comments, I am just refraining at the moment because I'll address that topic when, if and how I want to. :-)

Diana Moon said...

I got the link from Matt Metzgar's blog. Anyone can look it up. It's no secret he is Paleo but Atkins-skeptic. He has several links to studies that question LC dogma. I was just leery of putting anything that might seem as if I am stirring up a hornet's nest. Context is all.

carbsane said...

Posting for Jane who is having issues posting:

I was looking up 'fructose oxidative stress' and found something interesting. Even a small dose of fructose can cause oxidative stress, and it looks like free iron is responsible.

'A dose of fructose induces oxidative stress during endurance and strength exercise'
http://www.ncbi.nlm.nih.gov/pubmed/19763999

'Both in animal models and in humans, acute ingestion of fructose induces an early pro-oxidative state. Three molecular mechanisms have been involved in the disequilibrium induced by fructose: (a) an intrahepatic overproduction of lipid compounds and the subsequent generation of reactive oxygen species, (b) peripheral self-oxidation of triglycerides synthesized from fructose and with VLDL-c as a vehicle, and (c) the fructation of hemoglobin, which leads to oxidative reactions due to release of traces of Fe2+ via heme degradation, even in the presence of a physiological concentration of fructose. The present study was not designed to investigate the molecular mechanisms responsible for the oxidative stress after glucose plus fructose ingestion; however, we think that the last mechanism mentioned is the most probable to account for such fact due to the small dose of fructose administered in the glucose plus fructose beverages.'

Nigel Kinbrum said...

Dayum! You very nearly made me ruin my lap-top with drink!

carbsane said...

Metzgar's cool in my book. Don't always agree but that's not my yardstick.

PBJ said...

left leg is still intact

Nigel Kinbrum said...

Aw, you've gone and spoiled the joke! You did know that it was a joke, didn't ya?

George Henderson said...

BTW "significant" in this textbook is the difference between 5% and 10%, between 5% and 15%, between 5% and 25%. I didn't explain this very elegantly in my comment because the book is there, open, at the link to consult.

George Henderson said...

BTW "significant" in this textbook is the difference between 5% and 10%, between 5% and 15%, between 5% and 26%. I didn't explain this very elegantly in my comment because the book is there, open, at the link to consult.

carbsane said...

I wonder if the fat in NAFLD is recruited adipocytes in which case the increased oleic would make more sense in terms of the levels of production and the protective mechanism postulated in the book. Do you have this book? I would be interested in the references list for this section. The statement for the first highlighted instance of "palmitic" seems at odds with ... well ... I've never heard that before, and if oleic is the product of hepatic DNL why is the radio label incorporated into palmitic acid in Hellerstein etc.'s studies?


I know text revisions often take a bit of time, but I would think such a revelation regarding oleic being the product would be in the peer review literature ... very odd.

George Henderson said...

Interesting. There is a shift in desaturase expression which results in this increased oleate, quite possibly a protective mechanism. Don't have the book but I'd sure like it.
This confuses the issue; when is DNL not DNL?
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006066
"Interestingly, this higher lipogenic flux (+74 µg/g/h for oleic acid) in mice fed the high-fat diet was mainly due to an increased hepatic elongation of unlabeled palmitate (+66 µg/g/h) rather than to elongation of de novo synthesized palmitate."
Lipogenic flux? But I guess if the carbon from carbohydrate is going to lengthen dietary FAs, that's still DNL?

carbsane said...

I'm curious George why you think this confuses the issue regarding carbs.

Background

High-fat diets promote hepatic lipid accumulation. Paradoxically, these diets also induce lipogenic gene expression in rodent liver. Whether high expression of these genes actually results in an increased flux through the de novo lipogenic pathway in vivo has not been demonstrated.

Methodology/Principal Findings

To interrogate this apparent paradox, we have quantified de novo lipogenesis in C57Bl/6J mice fed either chow, a high-fat or a n-3 polyunsaturated fatty acid (PUFA)-enriched high-fat diet. A novel approach based on mass isotopomer distribution analysis (MIDA) following 1-13C acetate infusion was applied to simultaneously determine de novo lipogenesis, fatty acid elongation as well as cholesterol synthesis. Furthermore, we measured very low density lipoprotein-triglyceride (VLDL-TG) production rates. High-fat feeding promoted hepatic lipid accumulation and induced the expression of lipogenic and cholesterogenic genes compared to chow-fed mice: induction of gene expression was found to translate into increased oleate synthesis. Interestingly, this higher lipogenic flux (+74 µg/g/h for oleic acid) in mice fed the high-fat diet was mainly due to an increased hepatic elongation of unlabeled palmitate (+66 µg/g/h) rather than to elongation of de novo synthesized palmitate. In addition, fractional cholesterol synthesis was increased, i.e. 5.8±0.4% vs. 8.1±0.6% for control and high fat-fed animals, respectively. Hepatic VLDL-TG production was not affected by high-fat feeding. Partial replacement of saturated fat by fish oil completely reversed the lipogenic effects of high-fat feeding: hepatic lipogenic and cholesterogenic gene expression levels as well as fatty acid and cholesterol synthesis rates were normalized.

Conclusions/Significance

High-fat feeding induces hepatic fatty acid synthesis in mice, by chain elongation and subsequent desaturation rather than de novo synthesis, while VLDL-TG output remains unaffected. Suppression of lipogenic fluxes by fish oil prevents from high fat diet-induced hepatic steatosis in mice.



____________________________________________________


This effect is apparently induced by high (saturated) fat feeding, and appears to be compensatory/protective in nature. That carbohydrate might be the source of the carbons for elongation really doesn't make a case for the carbs turning to fat.


I don't know how relevant this is to human NAFLD, but it would seem to favor lower fat and saturated fat and higher O3 content in fat consumed.

George Henderson said...

When they say high-fat rodent diet they don't mean high-SaFA.

When they mean high-SaFA, they say it, as in this paper
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805500/

Long term highly saturated fat diet does not induce NASH in Wistar rats
Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats.


We also have intestinal DNL making a significant contribution to TG levels, as in this IR fructose study:

http://www.uoguelph.ca/hhns/grad/courses/HBNS6710/HHNS6710W09Haidarietal.pdf

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