Dophamn supplied the link to another interesting study:
The role of visceral and subcutaneous adipose tissue fatty acid composition in liver pathophysiology associated with NAFLD
Here is the money shot that supports the religion of saturated fat as the devil incarnate:
"Overall, these data suggest that diets enriched in saturated fatty acids are associated with liver inflammation, ER stress and injury".
Meanwhile, in the study detail:
I would agree that the stearic acid rats stayed comparable in weight to others despite eating more calories than either Crapinabag or PUFA fed rats, as in Table 1. There is NO evidence that they developed inflammatory changes in their liver! They had a statistically significant increase in messenger RNA expression for seven genes associated with inflammatory liver disease. The question is whether these mRNA changes actually result in detectable inflammatory changes in the liver, or are they markers of the normal response to reverse electron transport though complex I derived superoxide which might also trigger life extending increases in SOD and/or catalase gene expression? ROS generation is essential to mitochondrial biogenesis. It MUST affect signalling molecules. At what level does physiological signalling degenerate in to pathology? Easy to find this out, just look at the liver histology.
What we need to know is whether there is histological evidence of NASH development. After all, we know from the methods that they took terminal samples of liver and snap froze them in liquid nitrogen. Either sticking some in formalin at the same time or getting histology done on the frozen samples (not ideal from the histologist point of view but quite possible) would allow them to correlate their mRNAs with actual damage in the liver. They didn’t do this.
So why did they freeze liver samples at all? As they say in the methods:
“Liver tissue was homogenized in buffer (100mM Tris, pH 7.8) and alanine aminotransferase (ALT) concentration was determined from supernatant via manufacture instructions (Cayman Chemical, Ann Arbor, MI)”.
[Not my typo in the copy/paste. I can do enough of my own when I feel that way!!!]
In the results section in Figure 4 this is converted to:
“Plasma alanine aminotransferase concentration was higher in SAT compared with CON and PUFA”.
[My shouting emphasis on "supernatant" and "plasma"]
Plasma???? No. The methods clearly state that it was liver homogenate supernatant! Plasma ALT is an absolutely routine, standard, everyday marker of liver damage. It is a surrogate for hepatocellular damage, i.e. a normal component of liver cytoplasm which has leaked in to plasma in response to liver injury. It’s measured every day in any patient undergoing any sort of health/illness monitoring blood work. It is a COMPLETELY normal cytoplasm component while it is contained within the liver hepatocytes. It is LEAKAGE to the blood stream that we are interested in as a surrogate for hepatic damage. The rats all had terminal blood samples taken. The group could have measured ALT for a few pence in real plasma from this blood. They didn’t. They homogenised liver and measured ALT in the supernatant. They described this as “plasma”. All we can say from Fig 4 is that the liver of stearic acid fed rats has more of ALT within its hepatocytes. ALT is a normal enzyme used for interconverting certain components of the TCA/amino acid metabolism. Who knows why it is increased under stearate feeding, but it's not a marker of hepatocellular damage unless it is being released in to the blood stream... I think we can assume plasma ALT was completely normal. I'd be willing to bet it was measured in a pilot study and failed to pass the pay-dirt test.
The related studies cited in this paper are equally interesting and say nothing about much other than the ingenuity of the researchers. As always, my fascination is about the mindset involved.
Who decided to homogenise liver to get “plasma” ALT? Who decided to bin the histology friendly liver samples?