2008 Brain Star Award Recipient - Saima Malik
Saima Malik - Biosketch
Neurology & Neurosurgery
Ghrelin Modulates Brain Activity in Areas that Control Appetitive Behavior. Malik S, McGlone F, Bedrossian D and Dagher A. Cell Metabolism 7(5): 400-9, 2008.
Significance of the paper
Obesity is rapidly becoming the major cause of excess mortality worldwide. Therefore, understanding how the central nervous system regulates appetite and food consumption is of considerable interest. Ghrelin, a gut-generated metabolic hormone, is the most potent known appetite stimulant that signals hunger to the brain. Research in animals has established that this peptide activates the hypothalamic NPY/AGRP orexigenic pathway; however, ghrelin binding in brain regions associated with reward and motivation such as the ventral tegmental area and hippocampus, suggest that in addition to its role as a homeostatic cue, ghrelin may also modulate the hedonic and incentive aspects of ingestive behavior. In humans, very few studies have explored the effects of exogenous ghrelin on nutrient intake and energy balance, and no published work has offered insights into the CNS substrates that respond to this hormone to control feeding behavior. In this regard, we performed functional Magnetic Resonance Imaging (fMRI) in lean healthy males, to measure the effect of ghrelin on the neural response to pictures of food and scenery. We report that ghrelin administered intravenously during fMRI modulated brain activation to food pictures in structures involved in reward processing, motivation, memory, and attention; namely, the amygdala, insula, orbitofrontal cortex, striatum, hippocampus and pulvinar. This indicates that homeostatic feeding signals such as ghrelin may promote food consumption by enhancing the appetitive response to food-related cues. These results have clinical implications. Specifically, pharmacological blockade of ghrelin signaling might be a way to treat severe obesity.