Welcome all seeking refuge from low carb dogma!

“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact”
~ Charles Darwin (it's evolutionary baybeee!)

Tuesday, June 14, 2011

Where do triglycerides come from? Part II

Part I

Low carb dogma would have us believe that the triglycerides pumped out by our livers are not from the fats in our diet but the carbohydrates.  And specifically that they are formed from fatty acids derived from de novo lipogensis - DNL - aka excess carbs converted to fat.    As was discussed in Part I, in a whole food carbohydrate diet, DNL is not a major contributor to VLDL-triglycerides. 

So, now, we have additional work from the Hellerstein's research group at Berkley.  More specifically, a 2006 paper:
I'm going to discuss the paper and the results thereof in Part III, but for this installment I wanted to show and discuss a nice graphical overview of VLDL-TG sources from this more recent paper:

On the left side of the liver, we have all of the sources whereby fatty acids are supplied to the liver.  From the top down these are:  
  • Chylomicrons:  Chylos are the lipoprotein particles carrying dietary triglycerides.  The ultimate destination of the chylos appears to be the fat cells, but triglycerides can and are stripped from these particles en route.  When chylos become depleted of their triglyceride load they are then called chylomicron remnants.   A major function of the liver is to clear chylomicron remnants and repackage the triglycerides.
  • NEFA - Non-Esterified Fatty Acids, aka Free Fatty Acids - FFA:  As discussed in Part I, these are the major source of fatty acids for VLDL triglycerides.  Our fat cells are constantly cycling fats and delivering NEFA to circulation (and the liver).  This was discussed in detail in the paper that was the subject of this post, and shown in this schematic from that paper at right.   As indicated in the initial graphic, NEFA are increased/elevated in diabetics which is something we've discussed quite frequently here.  Lipoproteins (after being acted on by lipoprotein lipase) also contribute to circulating NEFA levels.  I would add an additional arrow down from the chylomicrons as dietary fats contribute to circulating NEFA when fat cells fail to appropriately trap and clear fatty acids liberated by lipolysis of chylo as discussed here.
In addition to these two exogenous (external to the liver) sources of fatty acids, DNL in the liver provides a third, albeit relatively minor, endogenous (within the liver) source.  All of these fatty acids are esterified in the liver into a combined "lipid pool" as I would describe that eliptical area in the center of the liver.

From there, the authors identify a "Delayed Secretory Pathway"  -- a holding tank, if you will, in the liver for triglycerides -- as compared to an "Immediate Secretory Pathway" where triglycerides from this lipid pool are packaged up and secreted immediately into circulation.  It would seem that fatty liver disease may well be associated with an increased shunting of triglycerides to the delayed pathway pool over the immediate pathway.  

In part III I'll discuss the results of the contribution of each of these two pathways to VLDL-triglycerides.

Continue to Part III


MM said...


So, from reading the paper it looks like most (~60%) of the TG are formed from NEFA. Do you think the reason low carb works for a lot of people to lower TG has almost nothing to do with lowering the DNL contribution, but just that they lose a significant amount of weight and that by itself lowers NEFA, which in turn lowers TG? The total contribution of DNL was a total of 13% for diabetics (only 3% for controls!), which doesn't seem like much to me. I can't see how only eliminating this pathway accounts for the significant drop in TG that a lot of diabetics see when they start on a low carb diet.

What do you make of the "unaccounted for" TG sources? I thought that was really strange. Where else could they possibly come from?

CarbSane said...

I'll address the unaccounted for TG's in Part III, but the authors did address possible sources in the study from Part I. Were I to speculate on why LC lowers fasting triglycerides it would be that it probably increases VLDL clearance rates (whereas in Part I they concluded that higher carbs reduced clearance rates rather than increased production). Also, perhaps, fewer NEFA are "trapped" by the liver and repackaged due to lower post prandial insulin incursions.

I posted on a study a while back that correlated fasting NEFA (rarely measured unfortunately) with LDL levels. So I would say those who see their LDL go up considerably (as often happens during weight loss and particularly at maintenance or regain) on low carb are probably just redistributing their circulating lipids.

I'm finding myself mostly in the camp these days that lipid particles themselves are not atherogenic, it's the excessive VLDL production that's a marker for metabolic mahem. Fasting trigs levels don't distinguish between production and clearance.

Mario Iwakura said...

And higher levels of fasting NEFA and LDL are also seen in hypothyroidism:

TSH seems to increase NEFA:

CarbSane said...

I'm a bit bogged down with my other efforts at the moment, but I will get to those links Mario.

In the meanwhile, I can't help but chuckle a bit at my Super Mario Brothers of thyroid I have commenting here!

Mario Iwakura said...


There is only one Mario commenting on this blog, and that one is me!

I misread the first study (20615126)... In fact, hypothyroid patients had 40% to 50% DECREASED concentrations of FFA (mean TSH was pretty high at 150mU/L).

Correct me if I'm wrong, but the interesting is that this does not fit some of your theories, since it's very well know that hypo patients have increased incidence of CVD, higher fat mass and impaired insulin sensitivity (p.e. and yet lower levels of NEFA!

CarbSane said...

It's gonna be a couple of days before I get to look at this stuff and comment. I'll probably just do a blog post on it. But there's a Mario Renato who has also commented on thyroid related issues here ... hence my "Super Mario Brothers" reference. Hope that didn't offend. :( ?

Mario Iwakura said...


For the third time: there is no other thyroid freak Mario commenting here! ;-)

My name is Mario Renato Iwakura! I just edited my Google profile to show my first and last name (and included a picture of one of my 4x4 trips to the Andes).

CarbSane said...

LOL, do I feel stupid. I'm a bit distracted at the moment with updating things here. I think I had a just Mario post here once too which was probably you as well. OK, so you're just Super Mario!

I did come across a while back that hypERthyroids have increased CVD risk and elevated NEFA. So this is quite interesting to me.

I think I've found an endo to get evaluated and see whassup with me. Meantime I'm sleeping like a baby these days. I do wake up sometimes but that's usually from going to sleep too early trying to keep my hubby's erratic schedule. Generally I fall right back to sleep. Selenium rocks!

Mario Iwakura said...

I'm glad you will have your thyroid evaluated!

Anyway, after you posted about your selenium experience, something similar occurred to me...

I never have had any sleep problems, but last year, when I was eating cod twice a week, I notice that I was weaking up to pee every night, something that never happened before. One month after I stopped eating cod (and increased the consumption of cilantro and
chlorella) because the mercury in it was increasing my thyroid antibodies, my sleep returned to normal (and my dry eyes too!).

Yesterday I received from Pubmed this study done in Tokyo residents that maybe can explain why you were selenium deficient:

"Although the analytical results suggested that the Se status of the subjects was generally adequate, as seafood was a major dietary source of Se, much of it was actually sequestered by mercury and only a fraction was bio-available"

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