Nonalcoholic fatty liver disease, once thought to be benign, is now regarded as a component of the metabolic syndrome and a likely precursor to non-alcoholic steatohepatitis, which can progress to liver cirrhosis in about 25% of patients, according to a University of Minnesota team.
The investigators found that among obese patients who ate foods containing radiolabeled fats five days before a scheduled liver biopsy, about 15% of lipids stored in the livers came from outside sources, Elizabeth J. Parks, Ph.D., and colleagues reported in the May Journal of Clinical Investigation.
The synthesis of fat from dietary carbohydrates was also found to be elevated in the patients during fasting but not after eating, when insulin would normally kick in to aid with glucose metabolism. This finding suggests a contribution by insulin resistance to excess fat accumulation in the liver.
"This is the first scientific proof of dietary fat stored in the liver in humans," said Dr. Parks. "In health, it's the liver's job to store glycogen -- a storage form of carbohydrates -- not fat."
She characterized the finding as representing "a clear implication that if one eats too much fat, as in the film Super Size Me, fat becomes deposited in the liver. This leads to a kind of liver toxicity that would be good to avoid."
Identifying the source of accumulated fats in the liver can help to improve current therapies and may provide new targets for future treatments, the investigators wrote.
There findings shed important light on the role that insulin resistance plays in liver disease, wrote Shinji Tamura and Iichiro Shimomura of Osaka, Japan, in an accompanying editorial.
"In light of these findings, it seems possible that the reduction of oxidative stress as well as the use of insulin-sensitizing agents such as thiazolidinediones and metformin may prove to be successful treatments for nonalcoholic fatty liver disease," they wrote.
To identify the source of triacylglycerols that accumulate in the liver and plasma in nonalcoholic fatty liver disease, the Minnesota investigators recruited nine obese patients who were scheduled for medically indicated liver biopsies. The patients were fed a diet containing stable isotopes of deuterium so that the investigators could trace how it was handled hepatically during transitions from the fasting to the fed states.
They found that the plasma pool of non-esterified fatty acids was the largest contributor to fats stored in the liver, followed by newly made fatty acids, and fatty acids derived from the diet. They also found that in the de novo lipogenesis was elevated in the fasting state and was not elevated following a meal as it would be in a healthy person, suggesting a contribution of increased insulin resistance.
- Reviewed by Ethan A. Halm, MD, MPH Associate Professor in the Departments of Medicine and Health Policy at the Mount Sinai School of Medicine in New York