Although scientists have long recognized that the hormone leptin plays an important role in obesity, Emory University researchers in separate studies are focusing on precisely how the hormone leads to weight gain as well as its relatively newfound role in cardiovascular disease and cancer. Produced in the fat cells, leptin is involved in a wide range of biological activities including appetite regulation, bone formation, reproduction and blood vessel formation.
Emory postdoctoral fellow Carmelo Blanquicett, PhD, studies the acute and chronic effects of abnormally high levels of leptin on vascular endothelial cells, which line the inside of blood vessels. Dr. Blanquicett has found that chronically high levels of appetite-suppressing leptin--levels found in obese adults--are linked to an important alteration in cellular signals in those endothelial cells.
Studies show that an association exists between obesity and an increased risk of cardiovascular disease; however, many of the mechanisms responsible for the increased risk remain unknown. Dr. Blanquicett's findings, presented at this year's Experimental Biology conference in Washington, DC, may help shed light on the mechanisms behind this association. More than 65 percent of adults in the United States are considered overweight, and 30 percent are considered clinically obese.
"Leptin works on the satiety center of the brain, where it exerts effects including the sensation of satiety, or fullness," says Dr. Blanquicett. "Ironically, obese people have unusually high circulating levels of leptin and as such are resistant to leptin's role of regulating metabolism," he says. Recent studies also suggest that leptin is involved in vascular function.
Dr. Blanquicett's research shows that prolonged high levels of leptin result in a desensitization of the signals that leptin produces in endothelial cells. These signals, which take effect with normal levels of leptin, cause blood vessel relaxation. In contrast, blood vessel constriction results in higher blood pressure and possible cardiovascular complications.
Leptin's role in breast cancer
In a second study, Emory University researcher Dipali Sharma, PhD, assistant professor of medicine, recently received a grant to investigate the role leptin plays in the formation and growth of breast cancer.
"Although leptin has long been linked to obesity, the hormone itself has only recently been found to play a major role in carcinogenesis, the transformation of normal cells into cancer cells. Obesity itself does not directly cause cancer," says Dr. Sharma.
"There's a hormone imbalance in obese patients," says Dr. Sharma. "Leptin increases the incidence of cancer, the aggressiveness of the disease and reduces the effectiveness of both chemotherapy and endocrine therapy in cancer patients. The only way to counteract this is to address the problem through different compounds and therapies, perhaps using a combination of approaches that includes standard treatments with new ones," she says.
Dr. Sharma's lab is now focusing on the basic mechanisms that control leptin's role in carcinogenesis. "Although leptin affects cancers such as those of the colon and endothelial tissue, it plays a major role in breast cancer because of the area's tissue composition. Breasts are composed of 90 percent fat cells and 10 percent epithelial cells," she says.
This study is supported by the Mary Kay Ash Charitable Foundation.