Visceral Fat & Hepatic Fat -- Not one and the same

It seems that any time the discussion of fatty livers developing on ketogenic diets comes around, a spate of confusing discussions tend to ensue.  One of the confusing issues is that ketogenic reducing diets are effective at reducing hepatic fat levels.  However, these studies usually start with a fatty liver and with weight loss comes hepatic fat loss.  If there's a study out there where obese people are simply transitioned from a SAD to an equi-caloric ketogenic diet (85+% fat) demonstrating any change in liver fat accumulation, I'm not aware of it.  However I believe the evidence of rodents on such diets is at least enough to be concerned that the change, if any, would be for the worse, not the better.  

A lot of lean people also think, I can't have a fatty liver because I don't have a pot-belly so I don't have visceral fat.  One of the reasons I thought the Eades' 6 Week Cure for the Middle Aged Middle  book was such a disaster is that the first two weeks were supposedly devoted to detoxifying your liver.  There were several references discussing just that, and a reduction in hepatic fat.  I had high hopes for the book at the time, because I was expecting some science on how to specifically reduce visceral fat.  I was disappointed that there was little if any discussion devoted to this topic.  Let's look at the human abdomen.  For starters, the liver is rather assymetrical.  Additionally, although obesity leads to a higher prevalence of fatty liver, lean T1 diabetics have a rather high incidence of the disease.  Roughly a quarter of those with fatty liver disease (FLD) have normal sized livers, so accumulation of hepatic fat does not necessarily increase the size of the liver.  A normal adult liver has a span of 7-10 cm and an enlarged liver is over 2-3 cm larger.  Still, this does not seem to be sufficient to cause a large belly.  Also note the location of the liver.  Most "bellies" are considerably lower.

Let's look at visceral fat depots.  That mauve thing in the diagram on the right there is the liver.  The "pot belly", as modeled by the fella on the left, is mostly omental visceral fat, and/or the front retroperitoneal visceral fat.  

While the woman at left here is likely packing some visceral fat, that "spare tire" roll around the middle is evidence of considerable subcutaneous fat.  While the guy above could probably squeeze some fat between a set of calipers, his tummy is likely relatively hard to the touch.  In any case, if either had an enlarged liver, it would be the proverbial "drop in the bucket" of overall fat mass.

I think this is a very important distinction to be made in discussions of insulin resistance as IR is associated with both hepatic triglyceride content and visceral fat accumulation.  Note I said associated as I'm not implying nor attempting to discuss causality here.  

In my recent post, I discussed two studies implicating a ketogenic diet producing a fatty liver in mice, I also discussed these previously.  In the second post, there is a table from the study showing that the triglyceride level of the keto-mice was higher than even the high-fat chow fed mice, despite growth and body mass similar to that of calorie restricted mice.  In the second protocol from the same study, the results -- where some high fat fed mice were switched to keto diets and lost body mass to equal normal (low fat, ~12% usually) chow fed mice.  However:  
Paradoxically, the increase in glucose tolerance and correction of lipid profiles occurred in the context of increased hepatic triglyceride content compared with both HF and C groups
Thus, since many employ ketogenic diets for weight loss, from a metabolic profile similar to the HFD mice, if not worse*,  the results of this study seem pertinent at least as cause for concern.  Since most folks eating a "ketogenic" diet are eating nowhere near the 90+% fat diet, the cause for concern is somewhat mitigated ... but perhaps if you are one of those humans with the "mighty metabolism" exhibited for these mice (10 &15% higher energy expenditure than standard chow and calorie restricted chow respectively), in other words you truly are eating more and losing or not gaining or whatever, then perhaps you might want to get your liver tested.  Elevated hepatic triglycerides occurred during growth of mice on KD and weight loss (then stabilized) after they were made obese on HFD.  It may be that during the loss phase, liver triglycerides were reduced, but they weren't after weight stabilized.

But ... but ... my belly got flatter!  (My own personal experience to the contrary aside ...)  Here is where this blurring of the distinctions becomes important.  Chances are if you gain or lose fat in your liver, we are not talking about a noticeable difference even if it is enlarged ... and it may well not be enlarged despite increased triglyceride content.  You may have lost a lot of visceral fat around your organs ... or just subQ fat outside of the abdominal wall ... but the two are not one and the same.  Therefore visceral or subcutaneous "slimness" is no reliable measure of your liver fat.  In addition, you are likely to "feel great" for a very long time!  The prevalence of some degree of FLD in Americans is shockingly high and it doesn't interfere with liver function for a good long time, certainly to any discernible degree.  You may be looking at several years or even decades before it progresses to a deleterious state.  Food for thought ...

* Coming from the SAD, being equivalent to the CAF diet, which was far worse than the standard rodent HFD, matters could well be worse for us humans.

Comments

bentleyj74 said…
Am I misremembering that in the crash diet you blogged about hepatic fat was decreased?
CarbSane said…
Nope, not misremembering ... both pancreatic and hepatic fat were reduced. I think the ketogenic diets shown to reduce hepatic fat in humans (I think it was Melchoir who cited the Spanish keto diet (that included 1-2 glasses wine per day I might add) as an example. This diet bears no resemblance to the diets these mice were fed. I think "ketogenic" is used far too broadly. Your standard VLC diet may up your ketone levels, but it's unlikely to be hyperketogenic at under 80% fat.
LeonRover said…
Epileptic keto diets are 85 to 90% fat.

I do not know whether NAFLD is a reported problem there with those complying.

I would also think that couple glasses of Rioja would be nice.

Slainte

PS those Ketoed mice have very odd enzyme levels.

"A unique metabolic state" - but do not count on upregulating human UCPs.
Galina L. said…
Recently I was present during a conversation between two women. One was my friend, another - a complete stranger to me, but a good acquaintance of my friend, so I was not comfortable to comment or ask questions. The lady-stranger complained to my lady-friend that since recently she often feels tired, started to gain weight, and her blood work showed an abnormal liver status. I immediately thought about a fatty liver decease. The lady with abnormal liver function didn't look fat in body, small-framed, with but noticeable double-chin and a puffy face, her loose outfit prevented more observations for my preying eyes.
There are suppose to be some indications that there is too much fat in somebody's liver.
bentleyj74 said…
So...where's all the folks who just couldn't wait for things to get more science oriented again? Someone say something incendiary.
LeonRover said…
"to wit, to wooo" ?
CarbSane said…
Hmmmm ... I've been thinking of pointing out that lots of high fat low carbers seem to have double chins. Some who have lost weight and developed a chin nonetheless. Some who are rather lean otherwise. Wonder if it is related to liver fat??
Galina L. said…
Changes of fat distribution suppose to be meaningful. I didn't noticed such pattern among LCarbers, but I am not watching them like you do. Very few not very young people I know who loose weight seems to have more loose skin under their chins, it especially noticeable in profile.
Mario Iwakura said…
It's interesting to note that those are symptoms of hypothyroidism and NAFLD (and NASH) has an increased incidence among persons with hypoT.

http://www.ncbi.nlm.nih.gov/pubmed/22183820
CarbSane said…
@Galina: One person who comes quickly to mind is Tom Naughton. He's not young, but not old either. If I watched Fat Head today w/o knowing it, I would think it was made 10 years ago. No ... 2008. In face shots, he looks heavier than he is -- while he has leaned out quite a bit. What I've noticed is that a lot of people eating high fat diets have the thick upper neck, less defined back of the jaw more than the double chin right under the actual chin (hope that makes sense).

@Mario: Interesting as always ... Update on me: thyroid normal.
Galina L. said…
Interesting observation. I noticed that vegetarians when they are not fat(it looks like there are different species - fat vegs and thin ones) and people who loose weight on low-fat diets often have a particular definition of the back jaw bone. So,it would be logical to say LCarbers have less of that definition. Tom's face doesn't look out of norm for me, probably, I should compare different images made in different years to notice your observation. On his pictures when he cleaned his house after renovation he looked pretty fit in a middle-body.
Lerner said…
I know that in the past, Eades had remarked that IFing could reduce NAFLD. When I went websearching for it just now, I did see something more recent about a study where the supposed best remedy was... (surprise, surprise) a lo-carb diet! There was a study cited and Parker was agreeing. However, since those people are advocates, I have learned to expect that they will never mention any study which supports a viewpoint different from their own.

That reminds of when I'd stopped visiting the lo-carb and Paleo sites, and then one day was reading about how the common way to induce NAFLD or HS in lab animals was by overfeeding FAT! I was surprised at something that in retrospect seems obvious because the LC and Paleo advocates had only ever mentioned fructose. The main lesson to be learned overall is not to trust advocates to be doing anything except arguing that they are always right and the supposed enemy is always wrong. (I'd assume the same applies to vegans.)

P.S. Nevertheless, one good thing about Eades was that I never saw him do the [crickets] routine of ignoring counterpoints. He would answer just about any counterpoint, even if his answer seemed unfounded.
Lerner said…
To my mind, the appearance of jowels is what indicates a person who does zero or too-easy exercise, regardless of their bodyweight.

Speaking of exercise, here's an interesting article on exercise and autophagy: "Exercise as Housecleaning for the Body"

http://well.blogs.nytimes.com/2012/02/01/exercise-as-housecleaning-for-the-body/

E.g., the "baseline level of cellular housecleaning wasn’t enough to protect [the rodents] from developing diabetes in the face of a poor diet. Only when the control animals ran and pumped up their intracellular trash collection did they regain their health".

and ' “I never worked out consistently before,” Dr. Levine says. But now, having witnessed how exercise helped scour the cells of the running mice, she owns a treadmill.'

The article also states that the researchers induced diabetes via a high fat diet. I noticed some of the comments saying "how can that be? We know that too many carbs causes diabetes". I used to believe that, too -- when I had been wandering around in LC re-education camps :)
bentleyj74 said…
"Only when the control animals ran and pumped up their intracellular trash collection did they regain their health."

I've wondered about this too not only in regard to exercise but also dipping in and out of calorie deficit.

"The article also states that the researchers induced diabetes via a high fat diet. I noticed some of the comments saying "how can that be? We know that too many carbs causes diabetes". I used to believe that, too -- when I had been wandering around in LC re-education camps :)"

Oy vey. Don't get me started.
Lerner said…
wrt fat and diabetes, from "global diabetes epidemic" researcher Dr. Meredith Hawkins at Einstein Med.:
http://www.einstein.yu.edu/video/?VID=30&ts=einsteinon&tsa=tabs-3#top

In the first minute, she talks about diabetes in rural Romania being caused by too much "pig fat".

(Later, she uses the term "malnutrition diabetes", which I haven't seen mentioned here. But that seemed a little sketchy to me, since that effect would also likely have occurred in previous 3rd world generations.)

Also from Einsten Med., here is autophagy researcher Ana Maria Cuervo, M.D., Ph.D. saying (at ~2:40 remaining) that most of what goes wrong with lack of autophagy garbage-collection is related to intracellular lipid:

http://www.einstein.yu.edu/video/slideshow.asp?VID=149
Lerner said…
quote Bentley: "I've wondered about this too not only in regard to exercise but also dipping in and out of calorie deficit"

For health purposes, I skip breakfast most days (except when I've lifted weights the night before and so crave meat, especially beef). Consequently, I've had hunger most every morning since June or so, but I just disregard the feeling. You're hot, you're cold, you feel the wind on your face, you feel hungry... all just feelings. Hunger isn't a command.

The ultimate healthwise might be working out while hungry.
"I just disregard the feeling. You're hot, you're cold, you feel the wind on your face, you feel hungry... all just feelings. Hunger isn't a command." Man, that amazing Dutch dude Wim Hof ("Becoming the Iceman") would totally agree with you. He's able to control his autonomic nervous system & how he responds to extremes of heat & cold by using a meditation technique that Tibetan monks do. He's convinced anyone can learn how. Hunger is controlled by the "lizard" brain as well, so I think you're onto something there.

Here's Todd Becker's interesting post about Wim: http://gettingstronger.org/2012/01/the-iceman/#more-3678
I spent two years teaching in Romania right after they finally ditched Ceaucescu. The pig fat, "Slanina" (spelling?) is considered a delicacy. If you're being feted, there's always a plate of it on the table. Sometimes it's julienned, sometimes cubed, often raw or smoked. I always figured they noshed on it to dampen some of the impact of all that local plum-brandy (Tzuica) they brew up in the bathroom & guzzle by the gallon.
bentleyj74 said…
Without listening to the lecture I can't comment intelligently but I will say I was pretty surprised at how poorly nourishing the average LC diet was. Average meaning "people who don't regularly consume liver and other organ meats". I expected pork roast and green veg to rate a bit better than it did to say the least [see LC re-education camp :P]. If they are eating huge amounts of fats relative to everything else where are the nutrients coming from? Just in terms of proportion it seems plausible.
Lerner said…
FTD, for me it's just a practical matter of attitude. Though I've mostly been a programmer, I've also worked construction. From being outdoors at 15F degrees, especially when you had to be still, I learned that when I was cursing the cold and pining for a roaring fireplace and a hot drink, that just made things many, many times worse. It's more practical to disregard the feeling. Practice helps a lot :)

The same goes for hunger or even for when I quit cigarettes a decade ago. My motto: Don't dwell on the physical feelings -- you can't fight yourself and win.

FTD, that was a fun article by Becker, thanks :) Once a year or so when hiking at a frozen lake with a thawed shore, I'll stand in the water barefoot. Those people there seem at Becker's somewhat like me :)

Btw, it does soon hurt like a thousand needles. I don't stay too long in it because once upon a time on a cold, windy day outdoors my finger went completely numb and that was very scary for 10-15 minutes.

Last year I made a video for someone in a southern state, to show what it's like walking around at zero degrees... which is different from Iceman in that moving makes your internal furnace come on and all was fine enough to even take my coat off... unless there is a strong wind.
http://visionals.info/video/ZeroDegrees.php

(though I know most people are afraid of clicking on links anyway)

I think I might like that Becker blog, though I hope it's not Paleo :)
CarbSane said…
@Lerner: If you search this blog on Becker you'll turn up an interesting exchange between us. He seems to have changed his tune on insulin somewhat in the intervening time as you will find on his blog -- perhaps I tweeted it.
@Lerner "I hope it's not Paleo :)" God I hope not! Actually, I was reading his About page and he seems to be more into the various forms of hormesis & trying them out on himself (to his non-paleo credit, I haven't yet come across any instances where he refers to his experimentations as "n=1" - if I do, I'm so outta there!). He strikes me as a Timothy Ferris type, just far less dopey & self-aggrandizing.
CarbSane said…
The Spanish ketogenic diet is not likely "ketogenic". While the ketostix have limits, I doubt I'd have registered back when I used them drinking wine daily for instance. These results tend to be in the short term during significant caloric deficit -- the FIRKO-ised mice ate the same amount roughly but lost weight. This is an example of where this study has its limits both pro and con on LC -- e.g. I don't really worry too much about your average LC'er b/c most aren't eating this high a percent fat in true keto-land.
CarbSane said…
@Lerner, there is considerable evidence that malnutrition in childhood leads to adult disorders -- apparently the women tend toward obesity, the men towards diabetes. All of the calorie restricted studies show the adaptation is for a reduced resting energy expenditure and partitioning of available energy to fat tissue (imagine that, still have to get to it, but low insulin favors such) vs. lean. If food then becomes available the women tend to pile on the pounds in the protective SAT while the men just exceed their visceral capacities and get diabetic. This is just a theory of course but lots of epidemiological evidence for it. I hope to blog on that sometime.

You can also become diabetic from starving or crash dieting. It's not common, but it apparently happens enough that "starvation diabetes" is discussed in the literature.
CarbSane said…
@Galina: When I first found LLVLC-land, it was shortly after that that the first pics from the 2009 LC Cruise made the rounds. I had no clue who Naughton was. I only watched Fat Head (it's free on hulu) for the first time about a month ago. A lot of pics were just from the mid-torso up. One's first impression of Tom -- well mine at least -- was that he was heavier than he actually is. He looked pretty slim in the belly in those recent pics (slimmer than in 2009). I don't know when FH was filmed exactly, maybe it took 5 years to make or something, but here I'm looking at changes in one person's appearance. We all age, but he looks a lot older than he did in FH. He also has a fatter face (neck) than he did then despite being thinner now.
Lerner said…
haha! FTD, I hate that "n=1", too :) It was clever 7 years ago when I'd first heard it, but let's give the term a rest and say some other phrase.

But uh oh... Becker's blog is moderated. I hate that, and usually never go back to a moderated forum or blog.

(I don't know much of Ferris.)
Lerner said…
@Evelyn: right, I believe it's possible, but not that it's more prevalent these days in the 3rd world. So therefore it's not a cause of the current 3rd world diabetes epidemic... oooohhhhhh, I get it: there always was the childhood or gestational malnutrition, but these days they are also later experiencing the higher level of adult feeding that hadn't happened in previous generations of adults.

Okay, my fingers have experienced enough typing-induced hormesis for now.
bentleyj74 said…
"I just disregard the feeling. You're hot, you're cold, you feel the wind on your face, you feel hungry... all just feelings. Hunger isn't a command."

Did anyone else just have the random urge to do a halo jump? [Hums guitar riff from pearl jam "Alive"]
cwaiand said…
i,ve often wondered why everyone is so against being hungry.i would think being hungry is about as paleo as you can get.low carbers are always against ever feeling hunger,they figure it,s the reason diets fail.i think it,s normal and we should not fight it by stuffing our faces the minute we fee lhunger.i think the frequent small meal camp did more damage than anything else.no cut back in your 3 squares a day but add in 3 or 4 "small "snacks.spells excess calories to me.
Sanjeev said…
> diabetes in rural Romania being caused by too much "pig fat".

shhhhhh .... Freddy baby might hear you.
CarbSane said…
I think I'm going to have to quote this one!!

Y'know cwaiand, I've always wondered over this obsessive hunger everyone's always talking about on diets. I'm not talking the 500 cal/day ones, I'm talking the regular ones. In my young ED days, it was OBSESSION over food that drove the bus to binging, blowing my self-imposed starvation, etc. It has nothing to do with hunger. And I do not understand all these overweight low carbers who claim they didn't eat too much on their SAD and couldn't lose weight on 1000 cal/day because of the hunger who remain overweight eating too much on low carb. Ahh well.

In addition to the frequent small meal camp (which actually worked well for me with VLC but I rarely ate a "meal" per se), I think the "breakfast is the most important meal of the day" and "never skip breakfast", "never skip a meal" because you're going to be hungry later and lose control and go apeshit. If I'm not hungry I don't eat!
bentleyj74 said…
"And I do not understand all these overweight low carbers who claim they didn't eat too much on their SAD and couldn't lose weight on 1000 cal/day because of the hunger who remain overweight eating too much on low carb. Ahh well."

Probably the most relevant example of self delusion re "healthy" food choices. Bravo. What's the difference between overeating and overeating on LC? Oh, well it might make a difference to your liver come to think of it...but aside from that...[drifts off muttering about not being hungry since Eisenhower was president and it's a good thing...completely healthy and normal...large fluffy LDL by the bucketful]
Galina L. said…
I like the idea of Becker's blog. For me it is about not being too soft - being able to handle stress, hunger, cold. The ideas of stoicism are appealing for people from Russia (and I am sure to many other populations), it is how we try to be in our family and how we were raised. Besides obvious things , I also think we should aim to tolerate pain better, be able to live without appliances, to fix what is broken, not to relay on a handful of medications to function, treat medical issues with a live-style choices without the regard how much it may be uncomfortable. I am glad I can tolerate hunger much better now, tolerating heat is still a challenge.
Galina L. said…
@cwaiand,
My guess, LCarbers are mostly people for whom LC diets work. I wouldn't be able to eat two times a day on another diet because now hunger is at tolerable level. I used to carry emergency food with me, had migraines because I didn't eat in time due to some emergency, in short, I had to keep food in mind in order to function, planed my day around meals. Definitely not paleo. Why to be ironic about such issues? Sometimes it is difficult to realized the magnitude of problem other people may have but you don't. I myself can't imagine how feel others who, for example, are scared of spiders or germs, or pay to their church 10% of their income because they are scared of hell or trust into another unproven hypothesis like going to heaven.
Lerner said…
How could you tell the difference between visceral fat and subcutaneous fat, let's say being blinded?

gross examination?
microscopically?
immunostaining?
do they have different organelles?
Unknown said…
This comment has been removed by the author.
Unknown said…
Response to Evelyn aka Carbsane - entry article:
"If there's a study out there where obese people are simply transitioned from a SAD to an equi-caloric ketogenic diet (85+% fat) demonstrating any change in liver fat accumulation, I'm not aware of it."

Here links to reports on US study showing that subjects on low carb diet lost significantly more liver fat than those on low calorie diet.
http://www.foodnavigator-usa.com/Science/Low-carb-study-could-lead-to-new-approach-to-fatty-liver
The low carb group also lost nearly twice the weight in the two weeks.
Here is to abstract of one more smaller study:
http://www.ncbi.nlm.nih.gov/pubmed/17219068
CarbSane said…
Thank you Sten! The foodnavigator study full text is available free here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701295/pdf/nihms-57436.pdf
This is a very interesting study for reasons other than the hepatic fat. I was surprised to see that gluconeogenesis doesn't use any more glycerol as substrate in VLC vs. -800 cal deficit diets.

I'm still looking for a study where weight loss was not involved. Hepatic fat is lost quite rapidly when one loses weight and both of your studies involved weight loss. What happens when weight loss stops or if one never loses weight?
Unknown said…
Evelyn, this study: http://www.ncbi.nlm.nih.gov/pubmed/15573908 compared degree of NAFLD with Fat and Carb intake prior to bariatric surgery. All subjects were of course morbidly obese so weight loss not relevant. The main study may correlate results with individual weights though. Liver inflammation correlated positively with carb consumption and negatively with FAT consumption according to food questionnaires filled in before operations.
The results supports the growing views that the international fat scare that emanated from the US in the late 1970's was scientifically poorly supported and are still today making people sicker instead of healthier. The basis for the low fat recommendations were associations without proper multivariate regression analysis that used cherry picked data, and no RCTs were conducted or reported.

Low Carb High Fat(LCHF) eating usually gives weight loss and a number of health advantages in the first few months, in part probably due to a more effective daily cleansing of the liver due to bile flow increasing in direct proportion to higher fat intake.
"Bile flow and liver status and other indicators during prolonged low/high fat diets" is a study I have been looking for without luck. Even 2 weeks could show results according to Brownings studies! But without weight change the longer time studies would be required to see differences as they naturally become smaller during weight stable conditions. Your question is good, but no complete answers yet:
"Is a standard high carb low fat weight stable diet affecting liver fats any different to a high fat low carb weight stable diet?"

In between the opposite- more carbs more NAFLD - has been reported. Nothing about weight change in the abstract:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661299/
Although here the correlation is with soft drinks that contain lots of fructose resulting in triglycerides when intake is an excess. If subject weights were collected and individually correlated with results your question could be answered, in part. If you find free link to this whole study, please post it!





CarbSane said…
More later in response, but your link to that soft drink study WAS to the full text! http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661299/
CarbSane said…
This is quite old, but visceral fat is defined as within the abdominal cavity vs. subQ is essentially attached to the skin. Abdominal fat is tricky though, as I've come across studies that distinguish types of subQ fat -- "deep" SAT -- that is metabollically distinguishable from more surface SAT. How do you tell that? I don't know!
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