Liver disease and triglycerides

Question

People who eat a large amount of fattening foods often develop fatty liver disease. People with fatty liver disease often have large numbers of small droplets of triglycerides throughout their livers. Having this disorder increases the likelihood of developing a large variety of liver diseases such as hepatitis, liver cancer, or cirrhosis of the liver. Why might fatty liver disease increase the risk for these conditions?

Alcoholics, regardless of their fat intake, often develop fatty liver disease. Here it is called alcoholic fatty liver disease. When alcohol is consumed, it is oxidized to acetaldehyde and then to acetic acid by NAD+. The acetic acid is mostly excreted through the urine or converted to acetyl CoA. The side products of this reaction stimulate fatty acid synthesis.

What side products are produced by alcohol oxidation? Why do these side products cause the synthesis of fatty acids? 

Finally, another cause of fatty liver disease is, somewhat nonintuitively, rapid weight loss. Given the livers many functions related to maintenance of homeostasis, why do you think this occurs?

Answer 1

Given that in a fasted setting with no free blood glucose or glycogen, fatty triglycerides are being readily converted into acyl-CoAs, which are metabolized into acetyl CoAs with the use of various ketones (a process known as ketosis). Such acetyl CoAs will assist with the breakdown of glucose from glycolysis upon their entrance into the citric acid cycle when the glucose has been converted into pyruvate.

In the case of excess alcohol consumption, there will be excess acetyl CoA in the cytosol as a result of the breakdown of ethanol. Since the cell will no longer require acetyl CoA (because it is in excess), beta oxidation of fat cells will cease. Hence, while alcohol does not "make" one gain more fat, it simply halts the breakdown of fatty acids that would occur in a normal setting.

On another note, fatty liver disease can be caused by rapid weight loss, as the liver's response to fat missing from the diet is the production of endogenous fatty acids.

All in all, everything in moderation.

Hope this helps.