Discovery Of Brain Circuits That Control Hunger Suggests New Targets For Treating Obesity

Main Category: Obesity / Weight Loss / Fitness
Also Included In: Neurology / Neuroscience;  Genetics;  Clinical Trials / Drug Trials
Article Date: 30 Oct 2007 - 3:00 PDT

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Researchers at UCLA have determined the brain circuits involved in hunger that are influenced by a hormone called leptin. In previous clinical trials, supplementation of leptin, the signaling molecule produced by fat cells, produced moderate weight loss in some obese patients, purportedly by inhibiting hunger and promoting feelings of being full. Thus, this new work suggests possible new targets for treating obesity.

Reporting in the Oct. 29 online edition of the Proceedings of the National Academy of Science, 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 report that leptin reduces activation in regions of the brain linked to 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 researcher's 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.

The reason the study only involved three subjects, said London, is because "having a genetic deficiency in leptin is extremely rare, so we were fortunate in finding them." Indeed, research published in 2005 by Julio Licinio, then at UCLA, used the same three family members to show that when leptin replacement was provided to them, body weight and eating behavior was normalized (Also in 2005, London and her team showed that leptin produced sustained changes in the tissue composition of the cerebral cortex in the same individuals.)

In order to determine the neural circuits through which leptin alters human feeding behavior, the researchers showed images of food to the adults both before and after leptin treatment, 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.

Despite the limitations in only having three subjects with the ob mutation, said London, "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."

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The research was supported in part by the National Institutes of Health and the UCLA General Clinical Research Center. During the course of this study Amgen, Inc., graciously provided leptin; Amylin, Inc., now provides leptin to these patients. Neither Amgen, Inc., nor Amylin, Inc., contributed to the design, analysis, or writing of this study.

Other authors involved with the study were John Monterosso, Tuncay Delibasi, and Anil Sharma from the Semel Institute and the UCLA

David Geffen School of Medicine, and Ma-Li Wong and Julio Licinio of the University of Miami Miller School of Medicine.

The Semel Institute for Neuroscience and Human Behavior is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective treatments for neurological and psychiatric disorders, improve access to mental health services, and shape national health policy regarding neuropsychiatric disorders.

Source: Mark Wheeler
University of California - Los Angeles

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