Recent advances in neuroimaging technology have given us the ability to detect brain function in vivo, noninvasively. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are the most widely used neuroimaging tools that provide brain maps of physiological changes (regional cerebral blood flow and/or regional cerebral blood oxygenation) as the brain responds to various stimuli. Presently, the typical human brain map obtained by these neuroimaging techniques, particularly fMRI, can achieve spatial resolution of ∼1 mm and temporal resolution of ∼1 second. These high resolution brain maps make it possible to study the dynamic features of the brain's physiological function.

Most recently, both fMRI and PET have been used to study human brain response to food intake. These neuroimaging studies have demonstrated that a significant difference exists in the response to the food intake between obese and lean people (1) (2). These differences include brain activity locations as well as timing and strength of the brain response. Gautier et al. (3), in this issue of Obesity Research, report additional evidence, using PET, to show different brain activity in obese and lean women in response to satiation. Although the phenomenon of different responses to food intake between obese and lean people was found, the exact mechanism causing this difference is not yet fully understood.

To understand the etiology of obesity, it is important to determine the role of the central nervous system in regulating eating behavior. It is well know that the hypothalamus plays a crucial role in basic life processes like feeding and drinking. In a previous study performed in our laboratory, we studied the effects of eating and focused on the correlation between fasting plasma insulin and a transient hypothalamic response (4). Our results suggest that circulating insulin levels modulate the brain activity that controls food intake, and this regulatory mechanism may be impaired in obese people (1) (2) (3). For more than two decades, insulin has been thought to be directly involved in regulating the central satiety signal (5) (6). Although studies in rats have demonstrated direct effects of insulin on the hypothalamic control of feeding (7), evidence in humans is still lacking. The important finding in the previous studies is a delay of the hypothalamic response after glucose intake (∼10 minutes in normal subjects and longer in obese subjects). Because the secretion of insulin increases immediately after a meal (8), our data suggest that insulin release may modulate the later brain response and that obese people may show a temporal discordance during these processes.

Correlation studies, in principle, cannot define a direct effect (i.e., insulin release may cause the hypothalamic response, the hypothalamic response may cause insulin release, or they may be parallel but independent). Rather, the question must be resolved by establishing a double dissociation of these events. That is, we need to block insulin release while testing for the hypothalamic response and, conversely, block the hypothalamic response while monitoring for insulin release. These experiments will be complicated, with many possible confounders, such as leptin levels, and will best be performed in animal models. Thus, it is very important that we have demonstrated a similar effect in an animal model, i.e., in rats (9). A possible next step is to chemically ablate the pancreatic β-cells of a rat (e.g., using streptozotocin) and repeat the imaging experiment to see whether the hypothalamic response remains intact. The results from future animal studies will likely answer the question of how the differential brain responses to the food intake between obese and lean subjects are related to the pathophysiology of obesity.

In short, neuroimaging studies from several laboratories have demonstrated that significantly different brain activity occurs in response to food intake between obese and lean subjects. Further exploration of the underlying mechanism that causes the difference may enhance our insight into obesity and its development.


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