Insulin is the key to keeping fat under control in the liver, even though it's been known for a long while that this hormone plays a role in fat production in the body. That new function for the well-known hormone was one of the important findings of a recent international study in the journal Cell Metabolism.¹

The new finding may help explain how the liver, frequently flooded with the fat-building hormone, normally stays trim. It also suggests new dietary strategies and treatments to help people avoid fatty liver, explained study chief Sonia Najjar, PhD, in the department of Pharmacology at the Medical University of Ohio, and her fellow researchers.

Obesity and Fatty Liver Disease
Fatty liver, known by its medical term steatosis, is a condition that falls in the category of non-alcoholic fatty liver disease (NAFLD). Steatosis can occur for a range of reasons, such as poor diet, certain illnesses, intestinal bypass surgery for obesity, or with certain drug use like corticosteroids.²

While simple fatty liver is typically a benign condition, it can lead to a much more serious complication known as non-alcoholic steatohepatitis (NASH), which is characterized by liver inflammation associated with its fatty makeup. This inflammation can lead to cell damage in the liver. NASH is not linked with other causes of chronic liver disease, such as viral hepatitis. It often occurs in middle-aged, overweight, and sometimes diabetic people who do not consume alcohol. Over time, the fatty tissue may break up liver cells, resulting in cirrhosis. Fibrosis, or liver scarring, can occur in up to 40 percent of people with NASH. Cirrhosis is common in up to 10 percent of those with the condition, according to statistics.²

"It has long been argued whether diabetes is a disease of glucose or fat metabolism," Najjar explained, in an e-mail interview with Priority Healthcare. "Therefore, investigation of how insulin resistance, the overarching predisposing feature of this condition, links these two branches of metabolism has been the object of intense investigation."

How Does Insulin Keep Liver Fat in Check?
The new study uncovered a mechanism in which acute pulses of insulin help limit fat buildup in the liver. Insulin does this by limiting the activity of an enzyme known as fatty acid synthase (SIN-thaze), which otherwise plays a key role in fat production in the body, Najjar said. This protective mechanism occurs "in the face of physiologically elevated insulin levels in the portal circulation," she said.

They found that insulin exerts its protective effect by activating a liver molecule. In rodents without this molecule, insulin wasn't able to control fat deposits in the liver.

Najjar and her colleagues tested the effects of liver-based insulin in a group of mice. In rodents that were obese or had persistently high levels of insulin, the hormone's protective function failed. This insulin breakdown is similar to what happens in people with a condition known as hyperinsulinemia (hye-per-in-suhl-ih-NEE-mee-uh), characterized by insulin resistance, resulting in abnormally high insulin levels. "In hyperinsulinemia, which is commonly found in obese and insulin resistant individuals, transient pulses of insulin are not remarkable, and the acute effect is abolished," Najjar told Priority Healthcare. "This leads to … fatty liver."

Ill Effects of Overeating
The findings also emphasize the liver's central role in the body's metabolism, the researchers underscore. A liver overwhelmed with insulin, as in those who overeat, may eventually become resistant to the hormone. This, in turn, leads to greater fat production and weight gain.

"When we eat, the pancreas produces insulin, which stimulates the absorption of sugar and fat by the liver," Najjar explained. "But in today's Western society, large portions and frequent munching may lead to insulin levels to remain high all the time. In that case, the liver no longer perceives pulses of the hormone and becomes resistant."

This scenario "is especially dangerous" for people with fatty liver disease in whom fat production is active, she said.

It's also characteristic in those with insulin resistance or type 2 diabetes. Insulin, produced by the pancreas, allows cells in our body to take up sugar from the food we eat, then burn it for energy. That's why in people with diabetes, the body's failure to make insulin, or its resistance to the hormone, causes sugar levels in the blood to rise. In the liver, however, insulin promotes the synthesis and storage of fatty acids and carbohydrates, and blocks their breakdown and release into the bloodstream.³

So far, abnormalities in the unique fat-blocking liver molecule uncovered in this study haven't been found in people diagnosed with insulin resistance or diabetes. But "it is tempting to speculate" that, somehow, the molecule's activity "might be compromised as a consequence or even a cause of the insulin-resistant state," wrote Alan Saltiel, PhD, a professor of Internal Medicine and Physiology at the University of Michigan, in a review paper accompanying the study.

If that is the case, finding ways to mimic the effects of the molecule might help alleviate chronically elevated fat levels in the blood and liver in those with diabetes, Saltiel predicted.

1. Najjar SM, Yang Y, Fernstrom MA. Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab 2005 Jul;2(1):43-53.
2. American Liver Foundation. What is NAFLD/NASH? Available at: http://www.liverfoundation.org/cgi-bin/dbs/articles.cgi?db=articles&uid=default&ID=1027&view_records=1. Accessed July 28, 2005.
3. National Diabetes Information Clearinghouse (NDIC). National Institutes of Health. What Diabetes Is. Available at: http://www.diabetes.niddk.nih.gov/dm/pubs/type1and2/what.htm. Accessed July 28, 2005.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.