Monday, February 12, 2018

Saturated fat and fatty liver. Payday in Sweden.

DLS posted a link to this paper in the comments on the last post.

Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans

It's really fascinating. It's rather the flip side to the rodent study in the post itself. They took reasonably healthy humans and over-fed them muffins based on palm oil or sunflower oil.

The core findings, here from the conclusions:

"The fate of SFA [saturated fat] appears to be ectopic and general fat accumulation, whereas PUFA instead promotes lean tissue in healthy subjects. Given a detrimental role of liver fat and visceral fat in diabetes, the potential of early prevention of ectopic fat and hepatic steatosis by replacing some SFA with PUFA in the diet should be further investigated".

And the most important finding from the results:

"the MRI assessment showed that the SFA group gained more liver fat, total fat, and visceral fat, but less lean tissue compared with subjects in PUFA group (Table 2)".

This is pay dirt. It completely justifies saturated fat avoidance at even modest overeating. As Tom Naughton has commented recently:

Jane Brody And The American Heart Association Bravely Admit They’ve Been Right All Along

Well. I guess we can all just pack up and go home right now.

But, ultimately, you have to try to understand what is going on.

So let's have a think about it. We have two populations of adipocytes in the two study groups. Each is being provided with an excess of fatty acids to store under the influence of insulin. One population is being exposed to palmitic acid. Palmitic acid provides the maximum FADH2 of all FFAs excepting stearic acid. So it predisposes to generating insulin resistance via reverse electron transport (RET). In adipocytes this means that they are less likely to accumulate triglyceride, ie palmitic acid stops you getting fat. It does this by limiting fat storage under peak insulin. My presumption is that, under free feeding situations, this information about the state of adipocytes is transmitted to the brain, either through plasma fatty acids, hormones or via the autonomic nervous system, resulting in a cessation of eating. But there is no cessation of eating allowed in the study. If you don't gain weight you are made to eat more muffins. You have to eat. If the excess fat in the diet is not going in to the adipocytes it is going to end up somewhere else. Liver and visceral fat are good places if you have nowhere else. Sticking it in muscles might well limit the anabolic action of insulin at this site.

The PUFA group are asked to eat more too. The linoleic acid in the muffins allows easy distention of this population of adipocytes (less FADH2 per unit NADH). Insulin acts easily because peak RET is blunted and adipoctes accept more fat. Excess dietary fat ends up in adipocytes, the adipocytes don't care. At 1.6kg weight gain in a young, fit Swede there is insufficient adipocyte distention to raise FFAs in the face of insulin.  Eating surplus PUFA appears to be metabolically easier to deal with than eating palmitate beyond acute needs. With sequestration of fatty acids in adipocytes rather than in to muscle we have the possibility for the anabolic effect of insulin actually working at increasing lean muscle mass.

We know that the groups were carefully managed to reach a very tightly controlled target of weight gain. Week by week the number of muffins fed per day was adjusted to give us the desired target gain of 1.6kg in each group. It took, on average, 3.1 muffins per day in each group to achieve this over seven weeks.

What we don't know is what the pattern of weight gain was during the study. Did the PUFA group gain weight easily in the early weeks and need less and less muffins later in the study to avoid excess weight gain, with the risk of overshooting the 1.6kg target?

Did the palmitic acid group show a steady weight gain, almost all of it ending up in ectopic sites because subcutaneous adipocytes didn't want to accept more fat throughout the study?

These are interesting thoughts. It is an interesting paper!

Peter

BTW There are a whole stack more questions regarding the role of fructose in the paper but I think the basics are probably covered in the differential effects of of fatty acids on the electron transport chain.

20 comments:

ctviggen said...

Peter, regarding the underlying theory for this article, what articles of yours would help someone just starting out with this theory? The Proton articles? Or is there a prerequisite before those?

Peter said...

Hi ctviggen,

The Protons thread is extremely waffly, especially at the beginning, but is the basis of the explanation for essentially all articles such as the above one. The problem is that there are layers of control systems overlaid on RET but my "belief structure" is that RET is primary for initiation insulin signalling at low nutrient levels and terminating it at high nutrient levels. It makes a great deal of sense so, in all probability, is wrong. Or not.....

Peter

jesrad said...

Reading the full paper...

"One individual from each group was excluded from the primary analyses due to considerable and unexplained weight loss during the intervention"

Extra ! Extra ! Read all about the new Muffin Diet that makes you gorge on processed crap while you effortlessly lose weight !

I'd love to interview those outliers, preferably over their full blood panels at start and end of trial.

"Food craving, hunger, and satiety were assessed in the morning (only at week 7) by the Food Craving Inventory and Visual Analog Scales, respectively."
"Food craving, hunger, and satiety showed no differences between groups (data not shown)."

Hmmm. Hmmmmmmmmmmmmmmmmmmmmmmmmm. Out of all the data otherwise presented.

cavenewt said...

It would be interesting to see a similar study comparing the effects of different fats, only with a low-carb diet. Because doesn't fat ingestion behave differently in the absence of carbs?

Muffins? Really??

Peter said...

jesrad, there is so much data which the group have in their possession but do not consider worth including in the paper. They either have the insight of a turnip or the paper is just a piece of advertising for bashing arterycloggingsaturated fat. With apologies to any turnips insulted by the comparison.

cavenewt: under VLC conditions insulin signalling is relatively unimportant and the differential between saturated fats and PUFA would tend to minimise. F3666 in rodents is about 30% of calories from PUFA, ketogenic and produces focal inflammatory changes in the liver. But it's not severe and doesn't shorten lifespan. Have the papers somewhere...

Peter

Peter said...

Oops, that would be "so many data"

DLS said...



An awesome read Peter! so basically... im doing the best # worst of both worlds eating surplus PUFA and SFA! -Unsure Larry David gif reaction- lol good 2 know pufa appears to be metabolically easier to deal with... at least regarding flab gain under stupid conditions... i still think there is something inherently bad with any -refined- substance regardless of composition and this my impact the results of the study: muffins are refined sugar? refined flour? refined crappy seed oils? also this logic also applies to butter, cream, fruit juices, etc etc

DLS said...

btw i took the liberty to contact mr Ulf Risérus
http://katalog.uu.se/profile/?id=N0-33

asking about the pattern of weight gain during the study n what group gained weight faster in the early weeks...


maybe well have an answer
lol

Peter said...

Hi DLS, The refined sugar is interesting. Once you consume fructose in high enough quantities (an Oral Fructose Tolerance Test involves 75g) you get high levels of systemic fructose, up to 5mmol/l. At this concentration it will induce a combination of palmitate generation and palmitate release from adipocytes. A significant proportion of the fats in fatty liver are from adipocytes in addition from the well known DNL source. Alcohol also shifts fats from adipocytes to liver and probably ectopic sites too. BTW did you see the odd result that both types of muffins depleted pancreatic fat???? That's really weird!

It will be interesting to see if Prof Risérus replies. And how...

Peter

altavista said...

http://www.smh.com.au/national/your-body-wants-to-be-fat-science-wants-to-change-its-mind-20180214-p4z0an.html

Peter said...

Hi altavista,

There are so many wrong assumptions in the article/from the researchers that it is impossible to get started. But humans are genetically adapted to get fat (at least for the last 30 years) and all that kept hunter gathers slim as lack of food. i.e., we were hungry all the time. I don't think so.

Peter

altavista said...

I agree. I sent it to highlight how the satiety information is (maybe) transmitted to the brain under free feeding.

jesrad said...

"did you see the odd result that both types of muffins depleted pancreatic fat?"

Nice catch ! Chalk up one more slogan for the Muffin Diet: it cures diabetes !

Am I reading Tables and 4 right ? It seems the SaFA group increased its PUFA/MUFA intake over the trial, whereas the PUFA group reduced their intake of SaFA. What would be the Protons meaning in those different situations ?

The P values in Table 3 look, hmm, convenient. And what of the alcohol intake discrepancy over the trial ? Did someone imbibe a muffin with rum (I know I certainly would have, makes it glide down the hatch all that more easily), lol.

cavenewt said...

I commented earlier about the difference between a high-fat diet with and without carbs.

A recent Peter Attia post addresses this somewhat. It's also a pretty good article about the importance of context. It's also very Peter-like in the way he examines the chow content.

"The HFD’s “key features” include “purified diet” and “diet-induced obesity.” The HFD by weight appears to contain just under seven times the amount of easily digestible sugars and more than three times the sucrose than the low-fat diet group by weight. Apparently, according to folks familiar with this diet, the mice won’t eat it without that much sugar in it. It seems the naturally herbivore mice didn’t evolve to find lard very palatable.

"...A recent systematic review of tumor cell growth and survival time with the ketogenic diet in animal models concluded that recent findings have shown that ketogenic diets might be able to inhibit malignant cell growth and increase survival. Taken together, the evidence suggests “high-fat” diets need more context, specifically the quantity and type of carbohydrates.

"A “high-fat diet” is not simply a high-fat diet. Specifying the level and type of carbohydrates and protein matter. People have done the research showing this and it shouldn’t be ignored (or missed).4 This matters not only for the tens of a percent of men with prostate cancer coupled with the loss of PTEN, but also for the general population."

https://peterattiamd.com/lack-context-may-fuel-spread-unintended-consequences/

Peter said...

Yes, the hallmark of most high fat diets is the sucrose content... Not quite always though, sometimes the linoleic acid can be enough...

Peter

Jason Jodway said...

Palm Oil seems to have some unique effects as a result of having a lot of free mono and diglycerides that get shuttled straight to the liver. I've seen atypical results when palm oil is used to generate a "high SFA" intervention in other studies and am always wary of any study that uses it now. It may be worth investigating that angle.

Peter said...

Interesting Jason...

Dophamn said...

Natural palm oil contains palmitic acid in a different triglyceride position (sn-1 and/or sn-3) than is typical in human/mammal/animal triglycerdies (sn-2). This means that it is less efficiently absorbed, since it forms "soaps" with calcium, which is also less well absorbed (thus lowering bone mineralization): e.g. https://www.ncbi.nlm.nih.gov/pubmed/9252903, https://www.ncbi.nlm.nih.gov/pubmed/20193141, https://www.ncbi.nlm.nih.gov/pubmed/28410612.

However, alteration of palm oil, to be more like a mammal fat, results in more efficient fat gain: e.g. https://www.ncbi.nlm.nih.gov/pubmed/23756564, https://www.ncbi.nlm.nih.gov/pubmed/21586170.

cavenewt said...

@altavista

The article you linked to ends with the following:

'Both trials were on mice, and it is relatively rare for animal studies to translate directly into humans, cautioned Dr Keiron Rooney, an obesity researcher at The University of Sydney.

'“And anyway, do we even want to be controlling our appetite with a drug? Are we happy to outsource an innate behaviour to a pill?”'

Dr. Rooney's career may not be long for this world. Two reasonable statements in as many sentences. Yikes.

Peter said...

cave, hahahahaha. And yikes too.