Fat May Promote Inflammation, New Study Suggests

“It is well known that obesity affects nearly one-third of adults in the United States and is closely linked with heart disease,” said Tongjian You, Ph.D., instructor in geriatric medicine at Wake Forest Baptist and lead author. “While we don’t fully understand the link between obesity and heart disease, our study suggests that inflammatory proteins produced by fat itself may play a role.”

The study, to be published in the April issue of the American Journal of Physiology – Endocrinology and Metabolism, evaluated whether inflammatory proteins produced by fat are linked to risk factors for heart disease, including high blood pressure, high cholesterol and how the body responds to insulin. The research is based on a new idea in medicine – that fat is an “organ” that produces proteins and hormones that affect metabolism and health.

The researchers studied two proteins that promote inflammation (interleukin 6 and tumor necrosis factor alpha) and a protein that promotes blood clots (plasminogen activator inhibitor 1). These proteins are all manufactured by fat tissue and involved in atherosclerosis, the buildup of fatty deposits in the linings of blood vessels. In addition, the scientists also looked at two “good” proteins, leptin, which regulates energy metabolism, and adiponectin, which has anti-inflammatory effects.

To gauge production levels of the proteins, the scientists took small samples of subcutaneous fat, which is just under the skin, from the abdomen and measured levels of messenger RNA (mRNA), which carries the genetic code instructions for cells to create the proteins.

The study included 20 post-menopausal women from 50 to 70 years old who were overweight or obese and had waists larger than 35 inches. Women in this age group are at increased risk for metabolic syndrome, a cluster of symptoms that increases the risk for heart disease. The syndrome is diagnosed when someone has at least three of the following: abdominal obesity, high triglycerides, low levels of high-density liprorotein (“good”) cholesterol, high blood pressure and increased levels of glucose (sugar) in the blood.

In 15 study participants without diabetes, higher levels of the “bad” proteins, interleukin 6 and tumor necrosis factor alpha, were associated with a lower ability to respond to insulin and use glucose. On the other hand, higher levels of the “good” protein adiponectin were associated with an increased ability to use glucose. Eight women who were diagnosed with metabolic syndrome – and had multiple risk factors for heart disease – had levels of adiponectin that were 32 percent lower than the 12 women who didn’t have the disorder.

“This suggests that low production of adiponectin in subcutaneous fat is linked with an elevated risk of heart disease,” said You.

The findings are significant because of the prevalence of both heart disease and obesity in the United States. Heart disease is the No. 1 killer in the United States, causing about 79,000 more deaths per year than the next five leading causes of death combined.

“It’s possible that modifying the inflammatory proteins through medication could also lower the risk of heart disease,” said Barbara Nicklas, Ph.D., senior researcher and an associate professor of internal medicine. “The findings point to a possible treatment target for new drugs. Our goal is to learn more about how these proteins are produced and how levels can be changed.”

Nicklas and colleagues have already begun a study to test whether diet and exercise will affects levels of the proteins. Scientists already know that weight loss and physical activity can reduce inflammation, but don’t know if this happens because the production of inflammatory proteins by fat tissue is reduced.

“We need to understand more about the mechanism,” Nicklas said.

The research was supported by the National Institutes of Health, the Wake Forest University Claude D. Pepper Older Americans Independence Center and the Wake Forest University General Clinical Research Center. Other researchers were Rongze Yang, Ph.D., and Dawei Gong, from the University of Maryland School of Medicine, and Mary Lyles, M.D., from Wake Forest Baptist.