This paper is an absolute gem:
Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars
Obviously you have to be very careful in reading it. It contains no trace of understanding in its entirety, but the numbers in the results are fascinating.
How do we sum it up?
If you pay people to over eat 1000kcal per day for three weeks they gain weight and they gain liver fat. The group eating extra butter/coconut oil gain the most liver fat (IHTG is intra hepatic triglyceride). From Figure 1:
Unsaturated fat (22% omega six PUFA) causes less IHTG accumulation than saturated fat, similar to an excess 1000kcal of (mostly) sucrose. So saturated fat is bad for your liver and PUFA or sucrose are less problematic. Shrug.
Aside: Almost no-one gets fat because they deliberately over eat. People get fat accidentally, bit by bit plus the occasional splurge, which they cannot then lose. In this study people did NOT accidentally get fat against their will. They over-ate because they were paid to, whether they were hungry or not. Any resemblance to real life is purely accidental. End of ranty aside.
So anyway, let's get to the interesting bit. Lipolysis. The group measured the rate of glycerol appearance, a perfectly reasonable surrogate for the release of FFAs from adipocytes. Under fasting conditions I think you would agree that saturated fat group increased their rate of lipolysis, just a trend, ns, over the three weeks.
Here are the changes in the rates of glycerol release under an hyperinsulinaemic clamp:
OK. Under an insulin infusion of 0.4mIU/kg/min, plus a bit of glucose, the adipocytes which have been exposed to saturated fats are STILL releasing glycerol (and so FFAs). Eating a mix of olive oil, pesto and pecans for three weeks allows lipolysis to drop like a stone when you infuse insulin, p less than 0.01 between these two groups.
This is pure Protons in action. Saturated fat provides an high input of FADH2 at electron transporting flavoprotein dehydrogenase, so reduces the CoQ couple, so promotes reverse electron transport through complex I which will generate superoxide when the NADH:NAD+ ratio is high, ie under caloric surplus. Superoxide is the signal used for setting up insulin resistance, to stop caloric ingress. Beta oxidation of PUFA skips one FADH2 generation for each double bond present so they are crap at signalling insulin resistance by this mechanism. Even under caloric excess, insulin continues to act and packs more calories in to adipocyes. And it refuses to allow lipolysis. It even very slightly (and ns) reduces fasting lipolysis (in graph B above), when insulin is as low as it's going to get on the SAD (in Finland).
Now for some context.
What do we know about the adipocytes of the subjects at the start of the study?
The BMIs were 30, 31 and 33 in the three groups and of the 38 people involved in the study, 22 had impaired fasting glucose at admission.
So these people already have PUFA induced obesity plus complications. That means that their adipocytes have gravitated to a certain (large) size related to their absolute exposure to insulin combined with a PUFA enhanced insulin sensitivity. This adipocyte size is larger than it would have been had the adipocytes mounted the normal resistance to insulin's action which is provided by saturated fats. As caloric ingress made each adipocyte "full", this "fullness" should have be communicated from the mitochondria (as superoxide) to the adipocyte (as insulin resistance) and eventually the brain as satiety (that signal is VERY interesting, another day perhaps). Under PUFA any distended adipocyte does not feel "full", it behaves as if it is still hungry. Whole body hunger follows on from this. Thanks to the cardiological community and their love of PUFA.
Along come three weeks of palmitic acid (plus a few other nice saturated lipids). Now there is plenty of FADH2, a reduced CoQ couple etc etc and the adipocytes are suddenly able to resist insulin... They suddenly realise that they are grossly distended and there is now no way they are going to accept any more calories (even with insulin infused at 0.4mIU/kg/min). In fact, given this new-found "awareness" of their bloated size, they are going to off load as much lipid as possible, in resistance to insulin's bloating signal. This is why they release glycerol (and associated FFAs) in the face of an hyperinsulinaemic clamp...
Of course lipolysis is fine if you accept the fat from your adipocytes and stop feeling hungry, so stop eating. Developing adipocyte insulin resistance gets fat out of distended adipocytes, saturated fat delivers this.
Of course, if you are pouring FFAs out of your adipocytes but some clown is paying you to eat 1000kcal above your preferred daily intake, you are going to have to do something with those FFAs. Failing to take the chance of a hike to the top of some 1000kcal high hill, the fat will end up in your liver. The more lipolysis, the more fat in your liver. In real life you would simply eat less, we know that supplying small amounts of fat to the liver via the portal vein is a potent suppressor of appetite, at least in rats.
This why I love rodent studies of obesity. You cannot pay a mouse to overeat. Any obese mouse gets to be that way because it is hungry. If you make it hungry using linoleic acid to sequester dietary fat in to its adipocytes then its liver will be fine until adipocyte distension releases enough FFAs to then allow fatty liver to develop.
Sorry if all this sounds like a scratched vinyl record about Protons but people will take this current study as proof that saturated fat is bad for you, which is bollocks of course. Or simply as incomprehensible. One of my biggest problems is that the Protons concept provides a logical explanation for many of the "paradoxes" of different fat types. However it is something of a language of its own and I feel I have no shared vocabulary to explain what is going on with people who do not have the concept... Ah well.
BTW The sucrose arm is interesting too but that's another story for another day. You noticed the ns-reduced weight gain in the sucrose arm? I digress...