Previous experiments have shown that supplementation of leptin, the signalling molecule produced by fat cells, led to moderate weight loss in some obese patients, purportedly by inhibiting hunger and promoting feelings of being full.
According to researchers, their findings suggest possible new targets for treating obesity.
Edythe London, a professor of psychiatry in the UCLA Semel Institute for Neuroscience and Human Behavior, Kate Baicy, a graduate student in London's lab, and colleagues have reported that leptin reduces activation in regions of the brain associated with hunger while enhancing activation in regions linked to inhibition and satiety.
The findings suggest possible new therapeutic targets for human obesity, an increasing problem in adults as well as children.
The research team used functional magnetic resonance imaging (fMRI) to measure brain activity before and after leptin supplementation in three adults from a Turkish family who lacked the leptin (ob) hormone due to a mutation. Such a mutation in the ob gene causes leptin deficiency and morbid obesity.
London said that the reason the study only involved three subjects is because "having a genetic deficiency in leptin is extremely rare, so we were fortunate in finding them."
To identify the neural circuits through which leptin alters human feeding behaviour, the research team showed images of food to the adults both before and after leptin treatment, and while fMRI imaging was taking place.
After leptin replacement in these individuals, feelings of hunger induced by the images and activity in certain brain regions associated with hunger the insula, parietal, and temporal cortex were reduced, while brain activity increased in the prefrontal cortex, an area of the brain previously associated with feeling full or satisfied.
London said despite the limitations in only having three subjects with the ob mutation, "we think knowing the mechanisms by which leptin alters brain function in congenital leptin deficiency can provide understanding of normal leptin physiology. Ultimately, that may help identify new targets for the treatment of obesity and related metabolic disorders."
The new study is published in the Oct. 29 online edition of the Proceedings of the National Academy of Science.