Mitch Leslie in Science:
The patient who walked into Joel Lavine's office at the University of California, San Diego (UCSD), medical center one day in the mid-1990s didn't know how sick he really was. He was morbidly obese. A brownish blemish known as acanthosis nigricans sprawled over the nape of his neck and into his armpit, signaling that he probably had developed insulin resistance, a condition in which cells don't respond normally to the hormone that controls blood sugar. A biopsy revealed striking damage to the patient's liver: so much fat crammed into the cells that it squashed their nuclei and other contents. Cirrhosis, or severe liver injury, was beginning as scar tissue ousted healthy cells. The patient essentially had the liver of a middle-aged alcoholic. Yet he was only 8 years old. To Lavine, a pediatric hepatologist, it was clear the boy was suffering from nonalcoholic steatohepatitis (NASH). A condition usually associated with obesity, NASH results from excess fat in the liver and, as the name indicates, doesn't stem from the alcohol abuse that causes many cases of severe fatty liver disease. Because NASH can destroy the liver, patients can require a liver transplant or even die.
…Ultimately, says molecular biologist Jay Horton of the University of Texas Southwestern Medical Center in Dallas, fatty liver “is a disease of caloric excess.” The imbalance between calories consumed and burned triggers a complex series of changes that transform the organ's character. Many of the diet-derived fatty acids in the bloodstream make their way to the liver, which directs them to other parts of the body. “The liver is your traffic cop” for these building blocks of fats, says Elizabeth Parks, a nutritional physiologist at the University of Missouri in Columbia. But the organ itself typically holds onto little fat. For instance, Parks says, a fairly fit 70-kg man will carry about 14 kg of body fat—and only 125 g will reside in the liver. “