Fat From The Previous Meal Sets The Metabolic Table

After publication of The Croissant Diet, which promotes a diet combining highly saturated fat and starch for weight loss, I got a lot of questions along the lines of whether it mattered if fat was eaten before starch. Or maybe protein should be consumed first? The proposed mechanism of the croissant diet is that saturated fat causes fat cells to be insulin resistant which caused them to reject storing energy from blood glucose, fat, etc. Several questioned whether saturated fat could really be digested and transported quickly enough to shut down insulin signalling to fat cells before nutrient could be stored from the meal.

All of this enhanced the concerns I had voiced in “Introducing The Croissant Diet” about whether dietary fat was burned preferentially to stored fat. Is there a LIFO (Last In, First Out) mechanism for metabolism.

The LIFO Mechanism

Lambert and Parks 2012 review is a good place to start thinking about what happens to dietary fat after a meal. Their Figure 1 is as good of a summation of how dietary fat is treated as I’ve seen.

Fat, including dietary fat, is stored as “triglycerides” – three fat molecules attached to a glycerol molecule. Triglycerides can’t be transported across membranes. In your intestine, lipase enzymes cleave the fats from the glycerol backbone, separating them into “fatty acids” (FA) which can be moved into enterocytes through fatty acid transport proteins.

Enterocytes are the cells that line the small intestine. Once inside the enterocyte, the fatty acids have several potential fates including being burned (oxidized) for fuel. Most of them are “reesterified”, which simply means turned back into triglycerides, packed into large bundles called “Chlyomicrons” and released into the bloodstream. Fat cannot simply be released into the blood in any quantity because it is not water soluble. So the enterocytes convert a certain amount of the fat to phospholipids. Phospholipids are just fats with a phosphate group on one end. Remember the “phospholipid bilayer” from high school biology? That’s how cell membranes work. The fatty chains stick to each other in the middle along with fat soluble proteins. The phosphate groups move to the outside because they are water soluble.

So a chlyomicron is a blob of fat surrounded by a single layer of water soluble phosphate groups which allows it to happily float through the blood. This is the same way detergent works. The detergents have a fat soluble end that stick to fats and a water soluble end that make the fat blobs water soluble. Cool, huh? This is also the same way mayonnaise and butter work. This also explains the problem with term “artery-clogging saturated fat.” The saturated fat doesn’t float in the blood, it’s packed into a water soluble chlyomicron. Other fat soluble parts of food can be packed into chlyomicrons as well – cholesterol, Vitamins A, D, E and K, etc.

The chlyomicrons float in the bloodstream until they encounter an enzyme called lipoprotein lipase (LPL). The LPL is attached to the membrane of epithelial (capillary) cells in various tissues and it is the enzyme that cleaves the triglycerides back into fatty acids, which can then be taken up by the tissues. When chlyomicrons encounter LPL they “park” there for a while and unload their cargo as fatty acids. The tissues taking up the fatty acids have the option to store them away or burn them immediately.

When fat is oxidized in the mitochondria, it has to be first cleaved by a lipase enzyme. It is the fatty acid, as opposed to the triglyceride, that enters the mitochondria. It makes sense that cells taking up fatty acids would oxidize (some of) them immediately. But do they? The best way to tell is to feed someone fat that is radioactively labelled and see how quickly the fat is oxidized and released in the breath or urine. And indeed, dietary fat is already being oxidized in the body within two hours of being ingested. The following is a table from the same review article.

Within two hours of eating a mixed meal containing fat, 6% of that fat had been oxidized and the radiolabeled products released in either breath or urine. After 10 hours, 26% of ingested fat had been oxidized. Clearly, one does not oxidize 26% of overall body fat stores in a ten hour window, so the tracer studies show us that indeed there is a Last In First Out mechanism of preferentially burning dietary fat over stored fat as the nonesterified fatty acids enter the tissues.

Other things I learned from tracer studies: as much as 48% of ingested fat is oxidized in the first 24 hours and 98% of dietary fat is cleared from chlyomicrons in 24 hours.

The Triglyceride Holding Pool

If you look at the first figure you’ll see that the enterocyte on the left has a “TG Holding Pool”. What is that about? According to the authors:

This is the answer to the question of how can dietary fat be absorbed quickly enough to disable insulin-stimulated influx of calories into fat cells. It can’t be, so the enterocytes hold a little bit back to prime the pump for the next meal. If this is the first meal of the day, this first released pool of chlyomicrons disappear from the bloodstream very quickly. Look at the charts of chlyomicron concentrations in individuals after tasting fat (the full paper):

Within minutes of eating, blood levels of fat spike and then are cleared from the blood, presumably because they are taken up by tissues as fatty acids that will then preferentially burn them. This all happens before energy availability of the current meal becomes available as blood glucose or chlyomicrons. Where does the fat end up? This paper shows that chlyomicrons localize in tissues expressing LPL.

Which tissues express LPL? Fat tissues, skeletal muscle, the heart and the hypothalamus. LPL activity is highest in abdominal fat.

Putting It Together

In The ROS Theory Of Obesity I suggested that the mechanism for which long chain saturated fat produced mice with very little abdominal fat was by driving ROS production at the mitochondrial bottleneck which knocks out insulin signalling in adipose tissues and therefore prevents fat cells from switching from fat burning mode into glucose burning/fat storage mode. In my croissant diet experiment, the biggest change I noticed was a reduction of abdominal fat, where LPL activity is greatest.

I noticed during the experiment that the consumption of long chain fats created satiety, especially after the first days. Many others who have tried the diet have reported the same effect on satiety. Satiety is in part signaled by ROS generation in the hypothalamus, which also expresses LPL.


Within minutes of eating, your enterocytes release a quick burst of dietary fat from your previous meal in chlyomicrons. The fat in these chlyomicrons are rapidly taken up by tissues that express LPL and begin being oxidized immediately. Major sites of the oxidation of these fats include fat cells, especially abdominal fat, and the hypothalamus. This fat oxidation seemingly happens before the major blood sugar and insulin rise from the meal. If the fat consumed in the previous meal is long chain saturated fat, the initial fat burst will lead to decreased fat storage, especially in abdominal fat and increased satiation due to hypothalamic ROS production.

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