LONDON (Reuters Health) – Low serum concentrations of leptin lead to increased fat storage and obesity, according to a report in the November 1st issue of Nature.
"Leptin is clearly an important hormone involved in the control of human appetite and fat mass," Dr. Stephen O'Rahilly from Addenbrooke's Hospital, University of Cambridge, told Reuters Health.
Though complete leptin deficiency has been known to lead to obesity, the authors explain, the influence of variations in serum leptin concentrations above a minimal threshold had been uncertain.
Dr. O'Rahilly and colleagues therefore examined 13 subjects from three unrelated families whose heterozygosity for a frameshift mutation in the ob gene (which encodes leptin) led to markedly lower serum leptin concentrations than in controls.
Body mass index did not correlate with serum leptin concentrations in these individuals, the researchers note, unlike BMI in control subjects, which did correlate with leptin levels.
However, the low-leptin individuals had nearly triple the prevalence of obesity (76%) compared with normal controls (26%), the report indicates, and fat levels in heterozygotes (as measured directly by dual-energy X-ray absorptiometry) significantly exceeded the proportion of body fat predicted by BMI.
"Our findings show that a relatively small drop in leptin production may be sensed by the homeostatic feedback system that controls energy balance," the authors conclude, "with fat mass being increased in an attempt to restore leptin levels to some 'set point'."
"We don't know the extent to which leptin resistance versus relative leptin deficiency might play a role in common forms of obesity," Dr. O'Rahilly said in the interview. "Our data suggest that relative leptin deficiency might exist and might be potentially correctable."
Nature 2001;414:34-35.
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