In otherwise healthy teens, elevated levels of leptin were associated with artery walls losing elasticity, an early sign of cardiovascular disease. The finding sheds light on the role of leptin in the development of early vascular disease and suggests a physiological link between vascular disease and obesity, says lead researcher Atul Singhal, M.D., deputy director of nutrition at the MRC Childhood Nutrition Research Center in London.
Leptin is produced by fat cells and regulates appetite and metabolism. It can harm blood vessels and obese people have high levels. The stiffness of a person's arteries has a direct effect on the workload of the heart. In healthy individuals, the walls of the arteries expand and contract as blood is pumped through them. As arteries lose their elasticity, (distensibility) they become stiffer and do not dilate to their full diameter. This reduces blood flow and increases heart exertion.
Arterial distensibility is known to correlate closely with atherosclerotic risk, even from an early age. However, few studies have examined distensibility, leptin levels, and fat mass in children.
Singhal and fellow researchers chose to study teen-agers so they could evaluate the role of leptin on vascular changes early in the development of arterial disease, without the presence of contributing factors often present in an older population.
They studied 294 healthy adolescents, ages 13 to 16, with a range of body mass indexes. Researchers performed noninvasive ultrasound tests to examine their arteries, measure blood pressure, blood cholesterol, glucose, leptin and the inflammation marker C-reactive protein (CRP). The average leptin level was 2.8 micromoles per liter (umol/L) for boys and 10.2 umol/L for girls.
"There was an increase in arterial impairment with elevated leptin levels, regardless of body fat, blood pressure, low-density lipoprotein (bad) cholesterol, CRP, or fasting insulin levels," says Singhal. "Although we know obesity is associated with atherosclerosis, the actual physiological process linking the two is unknown. This study may help explain one such mechanism."
Researchers noted a strong inverse relationship between arterial distension and leptin concentrations. A 10 percent increase in leptin concentration was associated with a 1.3 percent decrease in arterial distension.
The results are consistent with studies of animals showing that leptin concentrations are an important factor in the relationship between body fat and cardiovascular disease. The study does not demonstrate a causal link between leptin levels and cardiovascular health, but rather an association, says the researcher. Establishing a causal relationship would require an experimental intervention, such as reducing leptin, which would be difficult to do in human subjects. In addition, an intervention study would not be able to examine the effect of long-term leptin elevation and vascular function, says Singhal.
"Our study suggests a way in which obesity decreases the elasticity of blood vessels, thus increasing the risk of heart disease," he says. "Preventing even moderate fatness in childhood may have a long-term benefit for the risk of heart disease."
An accompanying editorial describes the study as "intriguing" and notes that it is an important addition in understanding the link between leptin and cardiovascular disease. It was written by John P. Cooke, M.D., an associate professor of medicine and director of the Vascular Medicine and Biology Program at Stanford University School of Medicine and Roberta Oka, R.N., DNSc., assistant professor of nursing, UCLA School of Nursing.
"It will be important to determine the mechanism by which leptin impairs vascular compliance and to determine if nutritional or pharmacological interventions to reduce leptin levels and/or reduce leptin resistance can improve vascular compliance in these individuals," they say.
"Perhaps more importantly, the study represents yet another harbinger of the epidemic to come as widespread childhood obesity gives rise to an unwelcome epidemic of cardiovascular disease in this generation," say Cooke and Oka.
Singhal's co-authors are I. Sadaf Farooqi, Ph.D.; Tim J. Cole, Ph.D.; Stephen O'Rahilly, M.D.; Mary Fewtrell, M.D.; Mia Kattenhorn; Alan Lucas, M.D.; and John Deanfield, M.D.
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