Non-alcoholic fatty liver disease, or NAFLD, encompasses a range of liver diseases diagnosed in people who consume little or no alcohol and which are caused mainly by fats. In addition to chronic infection with hepatitis B or C, other risk factors for NAFLD include obesity, diabetes, elevated cholesterol and triglycerides, and certain medications.1
Now, a new study uncovers some of the sources of those fats found in the liver.2 It's also the first study to show that a significant proportion of the fat that accumulates in the liver in NAFLD comes directly from your diet.
NAFLD ranges from the more benign steatosis—or fatty liver—to non-alcoholic steatohepatitis (NASH), which is an inflammation of the liver associated with fat build-up. It differs from steatosis in that this inflammation likely causes damage to liver cells while steatosis probably does not. The condition is also associated with obesity, insulin resistance and diabetes.
Evaluating the Etiology
There is no known cause for NAFLD, and treatment includes losing substantial weight, and good control of type 2 diabetes with diet, medications or insulin.3 "Previously, fatty liver was thought to be benign," writes Elizabeth Parks, PhD, an associate professor at the University of Minnesota and her fellow researchers in the Journal of Clinical Investigation. "However, it has recently become clear that fatty liver is a precursor of the more advanced liver disease non-alcoholic steatohepatitis [NASH], a condition that may progress to cirrhosis in up to 25 percent of patients."
Parks' team consisted of collaborators from the Department of Food Science and Nutrition and the Department of Medicine at the university.
The origins of the fats that accumulate in the liver in people diagnosed with NAFLD have remained a mystery, and helping to answer these questions will go a long way toward efforts to prevent the disease, the study authors stated. "Depending on the major source of fatty acids, you could then target therapy," Parks told Priority Healthcare, in a telephone interview. For instance, if liver fat were derived primarily from dietary fat, a person would then know to reduce his or her fat intake as a form of therapy. If, however, dietary carbohydrates were being made into fat and then stored in the liver, it would obviously not be appropriate to reduce dietary fat intake and increase consumption of carbohydrates, Parks pointed out.
Tracking Fat Synthesis
To assess the origins of fatty liver, the researchers recruited nine patients diagnosed with NAFLD who were previously scheduled to undergo liver biopsies. They each underwent CT scans to measure body fat and were instructed to consume specific diets throughout the study. Using a special non-radioactive marker of dietary fat, the fats contained in the diets, once consumed, could easily be distinguished from fat already in the body.
Each patient then underwent tests to examine the sources of fatty acids in their livers. Blood samples were also taken to measure levels of blood lipids, or fats, in each individual.
Typical Disease Characteristics Found
Parks' team found that each patient had characteristics common to NAFLD; levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased (indicators of liver damage), levels of triglycerides in the blood were also increased, and there was evidence of insulin resistance. The latter is a feature of a condition known as metabolic syndrome, which also includes hypertension, high insulin levels, obesity and high cholesterol—all risk factors for type 2 diabetes.4
On assessing liver biopsy results, the researchers noted evidence of liver steatosis in all patients, liver inflammation in all but two patients, and liver fibrosis in half the subjects.
The investigators then determined that there were three sources of fats in each patient's liver: blood fatty acids, newly made fatty acids within the liver, and dietary fatty acids—as much as 20% of fats from the patients' diets were found in their livers, the researchers noted. "The bottom line is, this is 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,” said Parks.
Liver Dysfunction
The team also learned that these fats build up in NAFLD because the liver is unable to regulate changes in fat metabolism properly, which occur between fasting and feeding times in the day. "The buildup of liver fat comes from elevated, expanded stores of fat in the body as a whole, and then [what occurs in NAFLD is] the inability of the liver to keep up with the export of the fats that are originating in it or those entering it from the blood," Parks stated.
To illustrate that, in healthy people without NAFLD, fats made from dietary carbohydrates within the liver should show a cyclic pattern of higher and lower levels throughout the day, running parallel with dietary carbohydrate intake during and between meals. Instead, in NAFLD patients in the study, newly formed fatty acids from sugars were higher than what one would find in healthy people, and these fats were made throughout the day, Parks explained.
Because of consistently high insulin levels, typically found in people with insulin resistance, the liver is "turning on fat synthesis and keeping it on 24 hours a day," she speculated. But whether this is a cause of NAFLD or the effect of it is still unknown, Parks added.
In conclusion, the researchers wrote: "Efforts to treat NAFLD by improving insulin sensitivity to reduce peripheral fatty acid flux should be expanded to modulate liver [fat build-up] through dietary and pharmacological therapy."
Study Reaction
In an editorial accompanying this study,5 Shinji Tamura, MD, and Iichiro Shimomura, MD, in the department of Internal Medicine and Molecular Science at the Osaka University in Osaka, Japan wrote: "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 NAFLD."
The findings will also contribute toward efforts to better understand "the effects of diet, exercise and pharmacological therapies on the disease," they wrote.
In the meantime, Parks says she and her colleagues hope to launch further research to assess how certain interventions like exercise and insulin-sensitizing drugs affect the movement of these various fatty acids to the liver. "We'd like to take this another step because a good number of people are affected by this condition. I think this is a side effect of obesity and insulin resistance that a lot of people aren't aware of," she said.
1. Mayo Foundation for Medical Education and Research. Nonalcoholic Fatty Liver Disease. Available at: http://www.mayoclinic.com/invoke.cfm?objectid=8903EB68-8F95-4135-87D24C6EFF964A6E&dsection=4. Accessed April 27, 2005.
2. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005 May2;115:1343-51.
3. American Liver Foundation. What is NAFLD/NASH? Available at: http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1027&view_records=1. Accessed April 27, 2005.
4. Mayo Foundation for Medical Education and Research. Metabolic Syndrome. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00522. Accessed April 27, 2005.
5. Tamura S, Shimomura I. Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease. J Clin Invest 2005 May 2;115:1139-42.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
