Fat. We worry about it when bikini season comes around. Rarely do we think about it accumulating in our vital organs. But even skinny people can have fat in places it shouldn’t be, like the liver.

Fatty liver disease has traditionally been associated with obesity and diabetes. But it’s also common in people who are not overweight: researchers have found that one in three lean people has fatty liver disease. Karen Corbin is trying to find out why.

Click to read photo caption. Photo courtesy of Karen Corbin

Corbin, now a researcher at the UNC Nutrition Research Institute, decided to study fatty liver disease after years of work as a clinical dietician. She routinely saw patients with high blood pressure or heart disease, but they weren’t always overweight.   

One patient who came to her outwardly appeared very healthy—he ran marathons, ate well, and did everything his doctors advised. Despite all this, he had to take three medications to control his dangerously high cholesterol, and by his early 40s he had already undergone quadruple bypass heart surgery.

Another patient, a thin woman in her mid-30s who ate a reasonable diet, looked normal and healthy on the outside. But inside, fat clogged her blood. Her triglycerides, which should measure around 100 or 150, were at 7,000. She too had to be put on a stringent medication regimen. 

What caused these people to be at such high risk for fatal disease? Corbin knew it was more than just diet. Generic “healthful eating” recommendations were not enough to improve the numbers on their blood work. And she knew the causes weren’t the same for both patients, even though they had similar symptoms. Corbin started thinking about individualized nutrition—the idea that each body has its own set of nutritional requirements. This motivated her to pursue a doctoral degree to study how biological differences affect nutritional individuality.        

To do that, she joined Steven Zeisel and his team at the Nutrition Research Institute in 2009 to study nonalcoholic fatty liver disease. The disease was once thought to be relatively benign, but Corbin says that in combination with other metabolic stressors, like high blood pressure or high cholesterol, it may become a much more serious issue. Liver cancer rates have increased dramatically in recent decades, and fatty livers could be partially to blame.

When fat enters the liver, it is broken down or transported out by metabolic processes that can involve essential nutrients. Zeisel has found that choline is one of these nutrients. If the body doesn’t have enough choline, the liver won’t be able to export fat, leaving it to accumulate there and cause problems. Corbin looks at the variations in genes related to the metabolism of choline to determine whether a particular person is more or less susceptible to developing fatty liver disease.

To better understand these genetic variations, Corbin took a closer look at liver biopsies from volunteers who were at risk for the disease. When she grouped her subjects by genetic variations, she uncovered a pattern in the choline pathway that distinguishes individuals with very low versus very high levels of liver fat.  

Finding this genetic pattern is a big step. Corbin’s ultimate goal is to create a model that can predict a person’s risk level for liver disease. To do this, she’ll recruit more subjects and look for differences in genetic patterns among ethnic groups. Larger studies could help her refine the model to more accurately predict each individual’s risk.

“If we can do that from a genetic pattern, that is something that could be put into medical practice,” Corbin says. “It might help us not just assess disease risk but assess what type of nutrition intervention might be most beneficial.”

Karen Corbin is a research assistant professor at the UNC Nutrition Research Institute.