Tuesday, December 01, 2009

Cirrhosis and corn oil

I think it is becoming clear that the collection of problems known as metabolic syndrome appear to centre around liver pathology. I accidentally ended up in these posts via iron overload and MODY1 of all things. Anyway, here's an introduction to the strange world of alcohol research in lab rats.

First I've got to apologise for these next few posts. They are mostly based around rats, fed by surgically implanted gastric canulae, with bizarre diets formulated to be fed as a liquid by constant rate infusion 23 out of 24h a day. Don't ask me why the rats got an hour off! I have to admit that I personally think lab rats are more like humans than many other observers do, but that may be because I've had so many of them as pets over the years. These rats do a number of things which are supposed to be impossible and a number which are just interesting.

Before we go to alcohol, lets just look at saturated fat and weight gain. These diets are isolacoric to the nth degree. There is no need to correct for caloric intake. They all got the same, 23/7. So we are not talking appetite here, just calories in vs calories out. All diets were 45% fat with protein and carbs also held constant. The table doesn't specifiy but you can be certain that the carbohydrate will be glucose or a glucose precursor. If you are looking at alcoholic cirrhosis you're not going to feed fructose!

Table 1 gives you the diet composition. That 45% of calories from fat was either pure corn oil or had increasing amounts replaced by a mix of beef and MCT fats. The highest saturated fat group had 30% of calories from saturated fat and 15% from corn oil.

Table 3 gives you the weight gain. Just look at the control groups: "Eat" corn oil as your sole source of fat and you gain 5.5g/d. Replace some of that corn oil with 10% of calories from saturated fat and there is a similar weight gain but go to 20% of calories as saturated fat and weight gain drops to 4.9g/d and go to 30% of calories from saturated fat and weight gain is 3.8g/d.

Under isocaloric conditions, simply switching from something quite like butter or coconut oil to "heart healthy" sunflower oil will make you FAT. Of course if you are used to eating butter and someone cooked your eggs in yellow boot polish you might lose weight because you would spit the "food" out on the floor anyway!

The rats got no choice. Corn oil fattens relative to a beef/coconut fat mixture.

Now it's worth looking at the effect of alcohol on liver pathology. This is best shown in Figure 2.

Without alcohol the lipid composition of the diet has no effect on liver pathology (small black bars). Replace carbohydrate with ethanol and the lipid source of the diet determines you liver pathology. Corn oil is catastrophic. By the time you are eating 30% of your calories as saturated fat and only 15% as corn oil your liver is almost OK. I leave it to anyone's eye to follow the trend and think about a diet which has 45% of it's calories as saturated fat and none as corn oil.

To me the message is clear. In the presence of ethanol the determinant of your liver pathology is the amount of corn oil you "drink". Fish oil does the same, the next few posts all use fish oil.

If anyone thinks that fructose is different to alcohol in it's effect on the liver, you're wrong!

I think the Food Standards Agency in the UK must have some sort of shares in liver transplantation programs or hardware.

Oh, another aspect of this study; at a given level of corn oil the weight gain was always less in the alcohol group than in the control group. Alcohol calories were being substituted for carbohydrate calories. Alcohol is not insulogenic, carbohydrate is. I'd expect alcohol to be associated with less weight gain as blood insulin levels would be lower. Come back Gary Taubes. You wus right agin! Dr Jebb, it's not a closed system.



Jenny said...


This is very interesting. But I am always leery about these rodent models for human diseases because in the diabetic conditions I'm familiar with the rodent models have completely different genetic dysfunctions than do humans with the same condition.

Beyond that, there is the problem that rodents have very different pancreata and digestive systems than people. So while the finding here is interesting, the way you extend the finding in these rats to humans may be mistaken.

The Sprague-Dawley rats used here are a freak strain preferred for research because of their tame behavior. Their organs are smaller than those of wild rats and their genetic diversity very limited.

I have reviewed far too much rodent lipid research which does NOT carry over to humans to jump on this conclusion until I'm shown some human evidence to support it. It might be very useful but it might only also be relevant for rats.

Peter said...

Jenny, hence the apology for going rat. But we have to start somewhere and until the errant stupidity about saturated fat stops no one is going to get anywhere with fatty liver management if it is due to PUFA in combination with fructose and/or alcohol. There is a simple testable hypothesis here which goes a long way to explain why LC eating doesn't work to improve fatty liver on ultrasound/biopsy... A significant proportion of the LC community and probably everyone in a fatty liver study is likely to wary of palmitic acid... Which cures rats in these bizarre experiments.


Manne said...

So according to this I should just stop smothering everything in mayonnaise to raise the fat content of my food?

// Manne

Peter said...



Zbig said...

for a 2500 kcal diet these figures translate to:
protein: 228 g
fat: 89 g
- control: 197 g
- alko: 9 g
alcohol: (alko group only) 154 gram

so it looks like a bit unrealistic for humans (read: less protein and more fat make me immune to alcohol, that's my version :)))

Unknown said...

Hm they are doing an untra sound of my liver this week because there is something wrong with my liver numbers in blood test. I've been increasing my fat and have taken fish oil for a while now, so I'm anxious to read your next post on fish oil. I'm thinking I also should stop eating all the fat. Linda

. said...

"These rats do a number of things which are supposed to be impossible and a number which are just interesting."

I'd be interested to know what these interesting things are, if you feel like elaborating some time. I'm not sure if you mean their observed behaviour, or what they (i.e. their bodies) "do" when subjected to various experiments.

Peter said...

Zbig, yes, just use the rats as general principles guides...

Linda, as Kurt comments on the fish oil post, "lipid" includes all manner of unpleasant stuff squeezed out of seeds as well as good stuff from beef. Unfortunately Hyperlipid is title I'm quite fond of...

Hi Chainey, the interesting bit to me is that the degree of unsaturation of their diet influences their weight gain and the impossible bit is the reversal of hepatic fibrosis. It can be done in this model, it needs doing in people! I think it might well be possible.


vanwash said...

With respect to crestor and diabetes, 1)Crestor lowers LDL-true 2)LDL binds to endotoxins- true(i never knew that) So crestor indirectly increases endotoxins->liver inflammation->inhibition of insulin to bind to liver-insulin receptor-> turning off of gluconeogenesis by the liver->diabetes. Am I understanding this right?

jimpurdy1943@yahoo.com said...

Peter, you might be interested in this new global PR assault on butter, by one of the leading margarine companies. They claim that butter should be banned!

Maker of Country Crock says Ban butter!

Manne said...

And I just found this this morning in the UK news.


"Ban butter to save lives, says heart surgeon"

Peter said...

Manne, yeah, me too! Ugh. I emailed him Krauss' meta analysis!


Marco said...

Hi friends, I love these blogs about diseases and cities, when I was in college did a very good study called liver cells, where I learned a lot about this subject

Puddleg said...

When it comes to the alcohol - PUFA connection I have no trouble accepting these rats represent us well. The action of alcohol on the liver is the same as for humans, as you can see by the various markers used (ferritin, LPS activation, lipid peroxide products), and we are talking about a very mechanistic effect of PUFAs - lipid peroxidation - not a hormonally regulated effect.
If you shot these rats in the liver with a bullet you wouldn't hesitate to extrapolate the results to humans, and we are talking about something not too far removed.
Also, Nanji was stimulated to do this research originally by an environmental study showing protective effect of beef in areas of moderate alcohol consumption, and a increased rate of cirrhosis where pork consumption was greater (pork being higher in PUFA than beef - about 9-11%, compared to 3%), a study with only human subjects.