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Keywords:

  • brain;
  • functional imaging;
  • positron emission tomography;
  • magnetic resonance imaging;
  • satiation

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Objective: To investigate the response of the brains of women to the ingestion of a meal.

Research Methods and Procedures: We used measures of regional cerebral blood flow (rCBF), a marker of neuronal activity, by positron emission tomography to describe the functional anatomy of satiation, i.e., the response to a liquid meal in the context of extreme hunger (36-hour fast) in 10 lean (BMI ≤ 25 kg/m2; 32 ± 10 years old, 61 ± 7 kg; mean ± SD) and 12 obese (BMI ≥ 35 kg/m2; 30 ± 7 years old, 110 ± 14 kg) women.

Results: In lean and obese women, satiation produced significant increases in rCBF in the vicinity of the prefrontal cortex (p < 0.005). Satiation also produced significant decreases in rCBF in several regions including the thalamus, insular cortex, parahippocampal gyrus, temporal cortex, and cerebellum (in lean and obese women), and hypothalamus, cingulate, nucleus accumbens, and amygdala (in obese women only; all p < 0.005). Compared with lean women, obese women had significantly greater increases in rCBF in the ventral prefrontal cortex and had significantly greater decreases in the paralimbic areas and in areas of the frontal and temporal cortex.

Discussion: This study indicates that satiation elicits differential brain responses in obese and lean women. It also lends additional support to the hypothesis that the paralimbic areas participate in a central orexigenic network modulated by the prefrontal cortex through feedback loops.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Recent neuroimaging studies have explored the neuroanatomy mediating the perception of simple stimuli associated with eating behavior (1) (2) (3) (4) (5) (6) (7). In men, administration of a liquid meal preferentially activates the prefrontal cortex, while suppressing neuronal activity in several limbic/paralimbic areas (4). These responses may be modulated by postprandial changes in hormones/metabolites and were different in obese and lean individuals (4) (5).

In women, brain responses elicited by the sight of food have been previously described (1) (2) (3). In particular, in normal weight women the sight of high-calorie food, rather than low-calorie or nonfood items, was associated with an increased desire to eat and significant decreases in regional cerebral blood flow (rCBF) within the temporoinsular cortex (3). In a second study, the sight of food was associated with increases in rCBF in the right parietal and temporal cortices in obese but not in normal weight women (1). In obese women with binge-eating disorders, exposure to food was associated with increased feelings of hunger with greater increases in rCBF in the left hemisphere, especially in the frontal and prefrontal regions, compared with non-binge-eating obese and lean women (2). Finally, bulimic women have been reported to have hypometabolism of the prefrontal cortex and hypermetabolism of the temporal lobe (8). Consistencies among the above studies are not readily apparent. However, these data suggest that the emotional and physiological events preceding eating, which include but are not limited to the sensation of hunger and the cephalic phase responses (9), elicit preferential activity of the neuronal fields of the frontoparietal lobe and the temporoinsular cortex, which are modified by the obese condition and other eating disorders. However, very little is known about the responses of the women's brains to the ingestion of a meal.

In the present study, we investigated the functional anatomy of satiation (i.e., the response to a liquid meal after a 36-hour fast) in lean and obese women. Based on previous neuroimaging findings (4) (5) (6), we hypothesized that the hypothalamus, limbic/paralimbic areas, and prefrontal regions would respond to the administration of the meal and be differentially affected in obese and lean women.

Research Methods and Procedures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Subjects

Ten lean (BMI ≤ 25 kg/m2) and 12 obese (BMI ≥ 35 kg/m2) women, 21 right-handed and 1 ambidextrous, were recruited by newspaper advertisement. All women were studied in the follicular phase of the menstrual cycle. Subjects were in good health and not taking medication, as determined by medical history, physical examination, and laboratory screening tests. Alcohol and drug abuse (and/or history of substance abuse or addiction), endocrine disorders (including abnormal thyroid function and type 2 diabetes mellitus), hypertension, pulmonary, cardiovascular, gastrointestinal, hepatic, renal, and central nervous system disorders were excluded at screening. Behavioral or psychiatric conditions (claustrophobia, major depression, presence of psychotic symptoms, and bulimia nervosa) were exclusion criteria of the study and were screened for by using the Structured Clinical Interview for DSM-III-R. All subjects were admitted for ∼1 week to the Clinical Research Unit of the National Institutes of Health in Phoenix. Subjects were restricted to the research ward and were limited to sedentary activity for the duration of the study. The protocol was approved by the institutional review boards of the National Institute of Diabetes and Digestive and Kidney Diseases and Good Samaritan Regional Medical Center, and informed, written consent was obtained from all subjects before participation.

Experimental Protocol

Experimental procedures have been described previously (4) (5). Briefly, on admission all subjects were placed on a weight-maintaining diet (50% carbohydrate, 30% fat, and 20% protein). Body composition was assessed by DXA (DPX-l; Lunar Co., Madison, WI) and measurement of daily resting energy expenditure was performed for 45 minutes using a ventilated hood system (DeltaTrac; Sensormedics Inc., Yorba Linda, CA). Before brain imaging procedures, subjects fasted for 36 hours. Water and noncaloric, noncaffeinated beverages were provided ad libitum during the fast.

Imaging Procedures

Positron emission tomography (PET) and magnetic resonance imaging (MRI) procedures were conducted at Good Samaritan Regional Medical Center (Phoenix, AZ). An MRI of the brain was performed using a 1.5 Tesla Sigma system (General Electric, Milwaukee, WI) to rule out gross abnormalities and to allow anatomical identification of the functional findings as described below. Gross anatomical abnormalities were ruled out by visual inspection of the MRI scans by the investigator (J.-F.G.) and absence of any pathological findings was confirmed before analysis of the data by a neuroradiologist. For the PET procedure, a transmission scan using a68Germanium/68Gallium ring source was performed to correct subsequent emission images for radiation attenuation. During each scan, subjects rested quietly in the supine position without movement and were asked to keep their eyes closed and pointing forward. PET images of regional brain activity (counts/pixel/minute) were obtained in each subject using an ECAT 951/31 scanner (Siemens, Knoxville, TN). Before each scan, a 50-mCi intravenous bolus of15O-water was injected. Two scans were obtained at baseline and two after feeding with intervals of ∼10 minutes between scans. Blood samples were collected immediately after each scan for the measurement of glucose, free fatty acids, insulin, and leptin concentrations.

Feeding Procedure

A liquid formula meal (53% carbohydrate, 32% fat, and 15% protein; Ensure-Plus 1.5 kcal/mL; Ross-Abbott Laboratories, Columbus, OH) was administered orally to induce satiation. To eliminate possible confounding factors, such as tactile stimulation of the tongue and motor neuron activity, swallowing was consistently induced by administering 2 mL of water before each of the four PET scans. Between the PET scans in the baseline and satiated states, a peristaltic pump (IMED 980; Imed Inc., San Diego, CA) was set to deliver a liquid meal providing 50% of the previously measured daily energy expenditure over 25 minutes. Subjective ratings of hunger/satiation were recorded after each PET scan (10). To familiarize each subject with the experimental setting and minimize the risk of learning-related artifacts, the feeding procedure was repeated twice on the research ward before the imaging session.

Analytical Measurements

Plasma glucose concentrations were determined by the glucose oxidase method (Beckman Instruments, Fullerton, CA) and plasma insulin concentrations by an automated radioimmunoassay (Access; Beckman Instruments). Serum free fatty acids (FFAs) were determined by an enzymatic colorimetric method (Wako Chemicals, Richmond, VA). Leptin was determined by a solid-phase sandwich enzyme immunoassay (Amgen, Thousand Oaks, CA).

Image Processing and Statistical Analysis

Automated algorithms were used to align each subject's sequential PET images (11), transform PET images into spatial coordinates of a standard brain atlas (12), investigate increases or decreases in rCBF independent of variations in whole brain measurements using analysis of covariance (statistical parametric mapping) (13), and generate normalized t value (i.e., Z score) maps of increases and decreases in rCBF. To reduce type I errors, a critical Z score ≥2.58 (p < 0.005 uncorrected for multiple comparisons) was considered to represent statistically significant changes in rCBF. Automated algorithms were used to transform each subject's brain MRI into standard atlas coordinates (14) and to superimpose each Z score map onto the averaged MRI to allow visual inspection of the composite images. To directly test the hypothesis that obese subjects have a different pattern of brain activation, we tested the interaction between condition (before meal vs. after meal) and group (obese vs. lean) using statistical parametric mapping. Pearson's product moment correlations were used to test the relationship between state-dependent changes in rCBF in region of interest (ROIs) and state-dependent changes in plasma hormones/metabolites and subjective ratings of hunger/satiation. The ROIs were defined as follows. After identifying the coordinates of maximal rCBF changes in response to satiation in all 22 subjects, we defined an ROI as a sphere of 1.2 cm in diameter around the coordinates. In each ROI, a mean rCBF (normalized for the whole brain blood flow) was calculated in each individual. An interaction term (group × variable) was used to assess possible differences between lean and obese individuals in the correlation between changes in rCBF and variable of interest in each ROI.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The characteristics of the subjects are shown in Table 1. As expected, the increase in plasma insulin concentration induced by the meal was higher in obese subjects and the decrease in FFA concentration was more pronounced in lean subjects. Basal and postprandial subjective ratings of hunger/satiation were similar in both groups.

Table 1.  Physical characteristics, hormones, and metabolites before and after a liquid meal in 10 right-handed lean women compared with 12 right-handed obese women (mean ± SD)
 Lean n = 10Obese n = 12Meal effect p valueGroup effect p value
  • *

    Subjects reported ratings of hunger and satiation using a 100-mm visual analog scale.

  • Meal-induced changes and relative group differences were tested by ANOVA for repeated measures.

Physical characteristics    
Age (years)32 ± 1030 ± 7 0.6
BMI (kg/m2)23 ± 241 ± 5 0.0001
Body fat (%)26 ± 640 ± 2 0.0001
Resting metabolic rate (kcal/d)1280 ± 1601710 ± 390 0.004
Metabolites    
Glucose (mM)    
Before meal4.3 ± 0.54.7 ± 0.3  
After meal7.3 ± 0.96.7 ± 1.30.00010.054
Free fatty acids (mM)    
Before meal0.99 ± 0.250.85 ± 0.13  
After meal0.54 ± 0.180.72 ± 0.160.00010.0003
Hormones    
Insulin (μU/mL)    
Before meal2 ± 16 ± 4  
After meal38 ± 3076 ± 950.00010.009
Leptin (ng/mL)    
Before meal4 ± 345 ± 17  
After meal4 ± 247 ± 190.130.13
Subjective ratings*    
Hunger (mm)    
Before meal68 ± 3081 ± 18  
After meal23 ± 3013 ± 140.00010.053
Satiation (mm)    
Before meal13 ± 99 ± 13  
After meal73 ± 3383 ± 180.00010.28

Regions of the Brain Affected in Response to Satiation in Lean Women

In lean women, the administration of a liquid meal (satiation) was associated with an increased rCBF bilaterally in the vicinity of the prefrontal and occipital cortex and posterior cingulate (Table 2; Figure 1). Satiation also induced significant decreases in rCBF in the vicinity of the insular cortex, parahippocampal gyrus, thalamus, caudate, temporal cortex, midbrain, and cerebellum (Table 3; Figure 1).

Table 2.  Significantly greater increases in regional brain activity in response to satiation in lean and obese women
 Lean (n = 10)Obese (n = 12)
  Atlas coordinates*  Atlas coordinates* 
RegionBrodmann's areaxyzZ scoreBrodmann's areaxyzZ score
  • *

    Coordinates from the brain atlas of Tailarach and Tournoux (12), such that x is the distance in millimeters to the right (+) or left (−) of midline, y is the distance in millimeters anterior (+) or posterior (−) to the anterior commissure, and z is the distance in millimeters superior (+) or inferior (−) to a horizontal plane through the anterior and posterior commissures.

  • Z score ≥ 2.58, p < 0.005 (uncorrected for multiple comparisons).

  • Regions previously reported to participate in aspects of satiation in men (4, 5).

Dorsolateral prefrontal cortex     9, 465638162.86
       −2858282.96
Dorsomedial prefrontal cortex8, 9, 10060405.128, 9, 10260403.67
Ventrolateral prefrontal cortex47−3832−244.3010, 11, 47−3656−124.68
  3640−243.56 3258−125.07
Inferior parietal lobule     39, 40−62−62243.00
Posterior cingulate29−16−44203.11     
Occipital cortex18, 19−48−8442.961958−7443.81
  58−74−43.28 −52−8083.92
image

Figure 1. Images of brain responses to satiation in 10 lean (left images) and 12 obese (right images) women at +32 mm, +8 mm, −4 mm, and −12 mm from a horizontal plane between the anterior and posterior commissures (coordinates of the Talairach and Tournoux (12) brain atlas). The right hemisphere in each section is on the reader's right. Brain regions with significant increases in rCBF in response to satiation are shown in blue; brain regions with significant decreases in rCBF in response to satiation are shown in yellow. Bold colors represent the statistical level of p < 0.001 uncorrected for multiple comparisons; transparent colors represent the statistical level of 0.05 > p ≥ 0.001. Images were generated using positron emission tomography and MRI data. Color-coded images were superimposed onto an average of the subjects’ brain MRIs (gray scale image). The figure is intended for visual inspection only of several areas of the brain, including the dorsomedial prefrontal cortex (dmpfc), dorsolateral prefrontal cortex (dlpfc), anterior cingulate (ac), posterior cingulate (pc), inferior parietal lobule (ip), occipital cortex (oc), caudate nucleus (cn), insular cortex (ins), thalamus (th), middle temporal gyrus (mt), ventrolateral prefrontal cortex (vlpfc), frontal operculum (fp), prefrontal/orbitofrontal cortex (pfc/ob), parahippocampal gyrus (ph), nucleus accumbens (na), hypothalamus (hp), amygdala (am), and midbrain (mb). Group differences in brain response to satiation and relative level of statistical significance were calculated using statistical parametric mapping and are presented in Tables 4 and 5.

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Table 3.  Significantly greater decreases in regional brain activity in response to satiation in lean and obese women
 Lean (n = 10)Obese (n = 12)
  Atlas coordinates*  Atlas coordinates* 
RegionBrodmann's areaxyzZ scoreBrodmann's areaxyzZ score
  • *

    Coordinates from the brain atlas of Tailarach andTournoux (12), such that x is the distance inmillimeters to the right (+) or left (−) of midline, y isthe distance in millimeters anterior (+) or posterior (−) to theanterior commissure, and z is the distance in millimeterssuperior (+) or inferior (−) to a horizontal plane through theanterior and posterior commissures.

  • Z score ≥ 2.58, p < 0.005(uncorrected for multiple comparisons).

  • Regions previously reported to participate in aspects of satiation in men (4, 5).

Hypothalamus      −22−124.00
Thalamus 16−2283.89 4−18123.40
Anterior cingulate     32036283.63
Posterior cingulate     31−10−26363.98
Precuneus     182−68242.76
Putamen      286164.11
       −16−283.95
Caudate nucleus 228163.09 −10−2124.00
       81043.87
Parahippocampal gyrus27, 30−24−48−123.0730−18−4683.59
 3522−34−43.06 20−46123.35
Middle frontal gyrus     9, 46−262444.51
Middle temporal gyrus42, 22−60−34202.8822−54−4443.50
       32−46123.15
Prefrontal/orbito frontal cortex     47, 12, 11−2626−44.67
Insular cortex 262642.65 −42−16−43.60
       36−1403.56
Nucleus accumbens     25−14−6−124.37
       48−83.84
Amygdala      18−6−163.8
Midbrain 2−16−123.10 12−22−83.04
Cerebellum −24−50−203.54 −34−36−204.30
       34−58−203.33

Regions of the Brain Affected in Response to Satiation in Obese Women

In obese women, satiation was associated with increased rCBF in the vicinity of the prefrontal, parietal, and occipital cortex (Table 2; Figure 1). In addition, satiation was associated with decreases in rCBF in the vicinity of the hypothalamus and other limbic/paralimbic areas (hippocampus/parahippocampal gyrus, amygdala, nucleus accumbens, cingulate gyrus, insular cortex, and thalamus), temporal cortex, precuneus, caudate, putamen, midbrain, and cerebellum (Table 3; Figure 1).

Comparison between Obese and Lean Women

Satiation induced greater increases in rCBF bilaterally in the vicinity of the ventrolateral prefrontal cortex and frontal operculum in obese compared with lean women (Table 4). The satiation-induced increase in rCBF in the medial aspects of the prefrontal cortex was attenuated in obese compared with lean women. In obese women, satiation was associated with greater decreases in rCBF in the vicinity of the limbic/paralimbic areas (parahippocampal gyrus, insular cortex), frontal and temporal regions, and caudate nucleus (Table 5).

Table 4.  Significantly greater increases in regional brain activity in response to satiation in obese compared to lean women
  Atlas coordinates* 
RegionBrodmann's areaxyzZ score
  • *

    Coordinates from the brain atlas of Tailarach and Tournoux (12), such that x is the distance in millimeters to the right (+) or left (−) of midline, y is the distance in millimeters anterior (+) or posterior (−) to the anterior commissure, and z is the distance in millimeters superior (+) or inferior (−) to a horizontal plane through the anterior and posterior commissures.

  • Obese vs. lean; Z score ≥ 2.58, p < 0.005 (uncorrected for multiple comparisons).

  • Region differentially activated in obese vs. lean men (5).

Ventrolateral prefrontal cortex10−3460−42.70
Frontal operculum47−5836−43.82
Table 5.  Significantly greater decreases in regional brain activity in response to satiation in obese compared to lean women
  Atlas coordinates* 
RegionBrodmann's areaxyzZ score
  • *

    Coordinates from the brain atlas of Tailarach andTournoux (12), such that x is the distance inmillimeters to the right (+) or left (−) of midline, y isthe distance in millimeters anterior (+) or posterior (−) to theanterior commissure, and z is the distance in millimeterssuperior (+) or inferior (−) to a horizontal plane through theanterior and posterior commissures.

  • Obese vs. lean; Z score ≥ 2.58,p < 0.005 (uncorrected for multiple comparisons).

  • Region differentially activated in obese vs. lean men(5).

Insular cortex −44−18−42.97
Middle temporal gyrus39, 40−44−38242.77
Parahippocampal gyrus 20−44122.71
  −26−12−243.39
Caudate nucleus −4242.92
Inferior frontal gyrus44−504283.23
Inferior temporal gyrus37−34−38−203.3

Correlation between Postprandial Changes in rCBF, Metabolites/Hormones, and Subjective Ratings of Satiation

Correlation analyses were performed in all brain regions that showed rCBF changes in response to the meal in the 22 women. Table 6 shows all correlation coefficients that were significant (p < 0.05) for any of the groups tested and/or correlations for which a significant group effect was identified. According to our analysis, the correlation between postprandial changes in FFA and rCBF in the right hippocampus/parahippocampal gyrus, left ventral, and dorsomedial (bilaterally) prefrontal cortex was different in lean and obese women. For glucose and FFA, opposite correlations for lean and obese women were observed in the right hippocampus/parahippocampal gyrus and in the dorsomedial prefrontal cortex, bilaterally (Figure 2).

Table 6.  Pearson's correlation coefficients (and p values in parenthesis, uncorrected for multiple comparisons) between changes (post-meal values − pre-meal values) in hormone/metabolite concentrations or satiation ratings and changes in rCBF in regions of interest defined as a sphere (1.2 cm in diameter) around the greater changes in rCBF in response to satiation obtained from 22 subjects (10 lean and 12 obese women)
 Obese subjectsLean subjectsAll subjectsGroup effect*
  • *

    Interaction term (group × variable).

  • Consistent with findings in men (5).

Region of interest with decreased rCBF in response to satiation    
Independent variable    
Ventral prefrontal cortex (left)    
FFA0.70 (0.02)−0.47 (0.17) (0.004)
Hippocampus/parahippocampal gyrus (left)    
Insulin0.64 (0.03) 0.44 (0.04) 
Hippocampus/parahippocampal gyrus (right)    
Glucose−0.31 (0.33)0.79 (0.006) (0.008)
FFA0.49 (0.13)−0.58 (0.08) (0.02)
Putamen (left)    
FFA0.62 (0.04)   
Posterior cingulate/precuneus    
FFA  0.49 (0.02) 
Satiation ratings  0.50 (0.02) 
Thalamus (right)    
Glucose 0.73 (0.02)  
Insular cortex (left)    
Glucose 0.67 (0.04)  
FFA −0.69 (0.03)  
Nucleus accumbens (left)    
FFA0.71 (0.01)   
Cerebellum (right)    
Glucose  −0.43 (0.05) 
Region of interest with increased rCBF in response to satiation    
Independent variable    
Dorsolateral prefrontal cortex (left)    
Satiation ratings  −0.43 (0.04) 
Dorsolateral prefrontal cortex (right)    
Glucose0.64 (0.02)   
FFA−0.65 (0.03)   
Dorsomedial prefrontal cortex    
Glucose0.77 (0.003)−0.62 (0.05)0.37 (0.09)(0.0007)
FFA−0.72 (0.01)0.07 (0.85)−0.50 (0.02)(0.04)
Occipital cortex (left)    
Insulin−0.68 (0.02)   
Occipital cortex (right)    
FFA−0.65 (0.03)   
Insulin −0.66 (0.04)  
image

Figure 2. Correlations between changes in plasma glucose (upper panel) and free fatty acids (lower panel) elicited by satiation and changes in rCBF in the dorsomedial prefrontal cortex, centered around x = 2, y = 60, z = 40 (coordinates of the Talairach and Tournoux (12) brain atlas). ▴ = lean women, • = obese women. Changes in plasma metabolites and rCBF are calculated as the difference between the post- and the pre-meal values.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

In the present study, we investigated changes in brain activity induced by satiation in women. Consistent with our previous results in men (4) (5), we found that the administration of a liquid meal after 36 hours of fasting is associated with increased rCBF in prefrontal and occipital regions and decreased rCBF in limbic/paralimbic areas, basal ganglia, temporal cortex, and cerebellum. Furthermore, we confirmed that obese individuals respond to satiation with greater activation of the prefrontal cortex and greater deactivation of some of the limbic/paralimbic areas compared with lean subjects. We also report satiation-induced deactivation in the vicinity of the amygdala and nucleus accumbens in obese women, which has not been previously reported.

We have previously suggested that activation of the prefrontal cortex may play an important role in the central regulation of eating. We have proposed that the prefrontal cortex promotes the termination of a meal by exerting inhibitory control on limbic/paralimbic areas, including the insular cortex, orbitofrontal cortex, and hippocampal formation (4) (5). This hypothesis is supported by observations indicating that the prefrontal cortex has efferent inhibitory connections to the limbic/paralimbic areas and exerts inhibitory control on brain activation in response to external and internal stimuli (15) (16) (17). Our findings in the brains of women are consistent with this model and confirm the greater activation of these cortical areas in obese compared with lean subjects.

The explanation for the greater post-meal activation of the prefrontal areas in obese compared with lean subjects remains unclear. Differences in postprandial excursions of macronutrients and hormones between obese and lean individuals may underlie the observed differences in brain response. The results of our correlation analyses are generally consistent with this possibility and even suggest an obesity-related effect of some hormones/metabolites on neuronal events. Alternatively, the greater neuronal activity of the inhibitory areas (prefrontal cortex) may simply be due to increased neuronal activity of the areas activated in hunger (limbic/paralimbic regions, etc.). Greater neuronal activity in the limbic/paralimbic areas and parietotemporal cortex in obese vs. lean women before rather than after the meal is consistent with previous reports (1) (2). Although differences in technology and data analysis prevent us from establishing the extent to which the results are neuroanatomically superimposable, two previous studies have reported that in non-bingeing obese women (1) and bingeing obese women (2), the sight of food, which in turn stimulates the sensation of hunger, is associated with greater increases in rCBF in the fronto- and parietotemporal lobes compared with controls.

We were unable to replicate the finding of an impaired hypothalamic response to a meal in obese individuals (5) (6). Although activation of the hypothalamus is part of our hypothesis, we have previously discussed the limitations in spatial resolution, contrast resolution, and the accuracy of the image deformation algorithm used to compute statistical maps, which limit our ability to detect significant state-dependent changes in regional brain activity in this small region of the brain (4) (5).

We have not previously observed deactivation of some areas of the dopaminergic system (nucleus accumbens, caudate, and putamen) and of the amygdala in response to a meal, which we observed in this study. Dopamine release in the brain is associated with pleasure and reward, and the dopaminergic system plays a complex role in eating behavior (18) (19). The amygdala has been shown to be activated in response to aversive gustatory or olfactory stimulation (20), and lesions of the amygdala result in hyperphagia and obesity (21). Additional studies are needed to formally test whether changes in neuronal activity of these dopaminergic areas and/or the amygdala are part of a gender-specific response to a meal.

In conclusion, our study indicates that satiation elicits differential brain responses in obese and lean women. It also lends additional support to the hypothesis that the limbic/paralimbic areas participate in a central orexigenic network modulated by the prefrontal areas through feedback loops.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

No outside funding/support was provided for this study. We thank Sandy Goodwin, Leslie Mullen, Tricia Giurlani, David Stith, Frank Gucciardo, and Burldean Anthony for technical assistance; Robert Hanson for statistical help; and the nursing and dietary staffs of the Clinical Research Center for their excellent care of those who volunteered for this study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References