Scott Grundy, director of the Center for Human Nutrition and chairman of the Department of Clinical Nutrition at the University of Texas Southwestern Medical Center, discussed "Obesity, Adipose Tissue Disorder, and the Metabolic Syndrome" at this year's Stare-Hegsted Lecture on March 13 in Snyder Auditorium. The event was sponsored by the Department of Nutrition.

Walter Willett, chair of the Department of Nutrition, introduced Grundy, calling him a leader in the field of lipid, or fat, metabolism.

Metabolic syndrome is thought to result from several factors including physical inactivity, bad eating habits, and genetics. Still poorly understood, the syndrome is gaining attention as more research is published. HSPH has contributed to the knowledge base, developing mice resistant to atherosclerosis and identifying a key gene in obesity and diabetes.

Some researchers have emphasized the relationship between the metabolic syndrome and the development of type 2 diabetes, said Grundy. But insulin resistance does not tell the whole story, he said.

Instead, heart disease may be a better framework in which to think about the metabolic syndrome, he said. At the Center for Human Nutrition, which he directs, research is focused on the metabolic syndrome and adipose tissue disorders, or fat tissue disorders. Grundy described the metabolic syndrome in terms of: adipose tissue overload (obesity); adipose tissue deficiency (lipodystrophy); adipose tissue maldistribution (abdominal obesity); and adipose tissue primary insulin resistance, which can result in diabetes. What do all four conditions have in common? They all are thought to increase the risk for heart disease.

Adipose tissue secretes a number of products, some of which seem to play a role in the development of the metabolic syndrome.

For example, one product of adipose tissue is nonesterified free fatty acids (NEFA). These acids are used by muscles for energy and by the liver, where they are regulated. Obese people have persistently elevated levels of free fatty acids, forcing the body to cope with the extra NEFA. How the free fatty acids are dealt with rests in part on where subcutaneous fat ends up getting deposited on the body.

Research at the Center for Human Nutrition indicates that fat collected in the upper or lower part of the body contributes to free fatty acids being directed to muscles. This can increase the risk for insulin resistance, according to one hypothesis, as NEFA interferes with the metabolic pathway that helps the body control glucose levels.

But fat that collects around the stomach, or visceral area, contributes to free fatty acids going straight to the liver. This abdominal fat has been implicated in an increased risk for heart disease. For example, a study in the December 4, 2002 issue of the Journal of the American Medical Association reported that men with metabolic syndrome--indicated in part by bulging stomachs--are at significantly greater risk of dying from a heart attack.

Obesity promotes the over-deposit of fat in the liver. The organ struggles to oxidize the overabundance of free fatty acids entering the liver, leading to fatty liver, part of the metabolic syndrome.

Even people with a clinical deficiency of fat tissue, a condition called lipodystrophy, are at risk for metabolic syndrome development, and therefore possibly heart disease, because their bodies lack a place to store excess fat. The fat gets inappropriately lodged in the liver and muscle. 

Grundy said although there are possible targets for pharmaceutical treatments of the metabolic syndrome, he would prefer an emphasis on changes to dietary and exercise behaviors.

The Stare-Hegsted Lecture is named after the late Fredrick Stare, the founding chair of the Department of Nutrition at HSPH, and D. Mark Hegsted, professor emeritus at HSPH.