Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis
This is how you really examine frozen liver samples for steatosis in a real laboratory:
"Neutral lipids in the liver were detected by Oil Red O stain. Liver cryostat sections were cut at 7 μm, fixed with 10% formalin for 5 minutes, and stained with Oil Red O in 2-propynal solution for 10 minutes"
The image on the right (for Ed to enjoy, even if the approach is a little basic compared to what you can do) is from one of the alcoholic mice, lots of lovely lipid accumulation:
And if you want to know about hepatocellular damage, you measure leaked ALT in real plasma from real blood:
"... the plasma ALT level was significantly higher in alcohol-fed mice (68.8 ± 17.0 U/L) than pair-fed mice (28.4 ± 6.7 U/L)".
No suggestion of homogenising liver and measuring ALT in the supernatant!
OK, so these folks seem quite honest and to know what they are doing. That's very nice.
What did they actually do? They deuterated the fatty acids in the adipocytes of live mice, got half of the mice drunk for a few weeks and then measured how much of the deuterated triglycerides turned up in the liver.
Lots did.
They also checked out why the adipocytes released their FFAs under ethanol. The mice developed whole body insulin resistance and they particularly developed adipocyte insulin resistance. If your adipocytes resist insulin, you get thin. Vodka makes you slim, while it grossly fattens your liver and makes you (mildly) insulin resistant.
As they say in the paper:
"In conclusion, the present study demonstrated that reduction of WAT mass and adipocyte size was associated with alcoholic steatosis. Activation of ATGL and HSL due to adipose insulin resistance is likely the major cause in alcohol-induced WAT reduction"
Speculation: Combining alcohol with a carbohydrate load (Beer!) will still make you "sort-of" slim, because any lipid you manage to force in to your adipocytes, using the hyperinsulinaemia needed to achieve normoglycaemia, will be released as soon as insulin starts to fall and you end up with a central beer belly combined with skinny arms and legs peripherally... Back to the paper.
The core slimming effect of ethanol is based on the induction of insulin resistance within adipocytes... This releases FFAs and the FFAs, if not utilised, are stored in liver and visceral adipose tissue.
You really have to wonder how much of the hepatic steatosis of fructose is generated in the same manner as that of alcohol, primarily driven by reverse transport of FFAs from adipocytes to hepatic cells. It would also be interesting to know if PUFA were released from adipocytes alongside the fructose-generated palmitate we talked about in the last post. The adipocytes certainly release multiple PUFA derived FFAs for transport back to the liver under the influence of ethanol.
Peter
BTW, did anyone notice that this group, who appear to be good, didn't measure or report plasma FFAs? I'm guessing FFAs are not markedly elevated in alcoholic reverse lipid flow, so trying to work out what is happening to lipid transport (or oxidation, for that matter) from FFA levels might be somewhat fraught, in any of those studies in which FFA levels are reported in the absence of isotopic tracking... Makes things tricky when you go on to think about fructose studies.
