Leapin’ leptin

Leptin is a secreted protein shown to regulate body weight in mice. It is encoded by the adipocyte ob gene. The leptin protein is postulated to be an “adiposity signal” affecting long-term regulation of body fat by the brain. As expected, leptin concentrations correlate positively with obesity and percent body fat in both women and men.

Leptin is also strongly associated with insulin concentration—insulin-resistant patients have higher leptin concentrations than insulin-sensitive individuals. An epidemiological study of 2537 men and women showed a strong association between fasting insulin levels and leptin concentration independent of obesity (as measured by body mass index and waist-hip ratio).

Leptin is also positively associated with systolic blood pressure and with C-reactive protein (a marker of low-grade chronic infection and a risk predictor for coronary heart disease). In a large study of Scottish males, A. Michael Wallace and co-workers reported that raised leptin levels show a post hoc correlation with the development of a coronary event (Circulation 2001, 104 (25), 3052–3056). Using blood samples obtained from the West of Scotland Coronary Prevention Study, the researchers compared multiple risk factors in 377 men who subsequently experienced a coronary event with those in 783 control men who did not. According to the researchers, “Leptin levels were significantly higher in cases than controls”—at least 16% higher. This correlation remained even after correction for the effects of age, lipids, and systolic blood pressure. The researchers concluded that this correlation makes leptin a useful circulating marker for percent fat mass and an independent correlate of insulin resistance that may yield new information on understanding the risk of cardiovascular disease. They do not believe that leptin has a direct effect on the vascular system and consider that it is too soon to incorporate leptin monitoring as a routine assessment for patient risk.