The present study was performed to examine sex-based differences in appetitive behavior as well as in the neuronal response to food-related visual cues. The results of this study demonstrate that across sexes, food-related visual cues result in activation of brain regions known to be important in energy intake regulation. Women, however, have a more robust prefrontal and parietal response to food-related visual cues than men. In addition, women appear to be more sensitive to food intake as indicated by increased post-meal satiety ratings. Women are more likely to maintain isocaloric intake during ad libitum feeding, whereas men are more likely to overeat. Furthermore, although measures of feeding and dietary behaviors do not predict subsequent energy intake, dorsolateral prefrontal cortical (DLPFC) response to visual food cues correlates with subsequent energy intake.
As we have previously shown, the neuronal response to food-related visual cues is complex associated with the activation of a network of brain regions, including the insula, inferior temporal visual cortex, posterior parietal cortex, ventral striatum, posterior cingulate, hippocampus, sensory cortex, and lateral prefrontal cortex[18
]. The activation of a number of these regions is consistent with increased attention to food cues and enhanced motivation to eat and implicates these regions as important in the regulation of food intake.
Similar to the findings of Uher et al[21
] we found a pattern of increased neuronal response to visual food stimuli in women as compared to men, supporting the hypothesis that women are more sensitive or `reactive' to food-related cues than men. Our findings suggest that women have greater attention (parietal response) and cognitive processing (prefrontal response) related to food stimuli. The greater DLPFC activation in women may also suggest a greater inhibitory response to the food cues. A more sensitive region of interest analysis also revealed greater response in women in the fusiform gyrus at the location reported by Uher et al[21
]. The present fusiform finding, along with Uher's finding of a fusiform difference during visual, but not taste food cues, is consistent with the notion that response differences in this region may be sensory modality- specific, relating to the visual processing of food cues[21
]. Other differences between our study and the Uher et al study may be due to the greater salience of the food cues in our study.
Wang et al found that while food stimulation (sight, smell, taste) as measured by PET was associated with higher whole brain metabolism in both sexes, women were unable to suppress, using cognitive inhibition, brain regions important in emotional regulation, conditioning and motivation to the same degree as men[29
]. Other neuroimaging studies have also found sex-based differences in the response to general cognitive and emotional tasks[35
]. These sex-based differences in neuronal responses could be due to differences in brain organization and/or to the use of different cognitive or emotional strategies.
What mechanisms underlie these observed differences in responses to visual food stimuli in women as compared to men? Certainly differences in sex steroids could be an important mechanism. Animal studies have shown that sex steroids have direct effects on specific brain regions such as the prefrontal cortex[38
]. Cortical responses during cognitive tasks in humans appear to also be associated with estradiol levels[36
]. In addition, sex-based differences in leptin action could be important. Animal studies have shown that estradiol alters leptin and ghrelin sensitivity[8
] as well as altering the anorexic/orexigenic responses to other mediators such as NPY and melanin concentrating hormone[42
]. Although one might postulate that these central effects would primarily impact homeostatic-related brain regions, fMRI studies examining leptin deficiency and replacement have shown that it can alter higher brain responses to food stimuli[44
]. Certainly these sex-based differences deserve further investigation and emphasize the importance of potentially studying men and women as separate groups.
We also found sex-based differences in appetitive behavior. As has been previously reported[14
], we found that women had greater dietary restraint than men. There was no sex-based difference in disinhibition, typically a better predictor of weight gain. We also found a sex-based difference in appetite ratings. When the diet was controlled, women reported greater post-meal satiety than men, suggesting greater sensitivity or reactivity to feeding. When “control” over the diet was removed this sex-based difference disappeared. Of greatest interest, though, was the sex-based difference in ad libitum intake. Women were able to self-select a diet to match their energy needs. Men, on the other hand, overate by over 300 kcal per day once study control was removed from diet. While these findings are consistent with the fact that women had greater dietary restraint we found no correlation between restraint scores and food intake. These findings could relate to women having higher levels of body weight and shape concerns as well as greater social and cultural influences[17
]. The subjects in this study were not dieting and were screened to be free of eating disorders.
Finally, we hypothesized that an individual's baseline feeding and dietary behavior might impact subsequent energy intake, and therefore examined the relationship between baseline measures of restraint, disinhibition, appetite and subsequent ad libitum energy intake. Interestingly, none of these measures correlated with subsequent intake, nor did any of these measures correlate with each other. In other words, these `qualitative' measures of food intake and behavior were poor predictors of energy intake. Some preload studies have shown that qualitative measures of appetite do not predict subsequent energy intake[47
]. Other longer-term diet studies have also shown a lack of correlation between appetite ratings and intake[18
]. Additionally, it has been shown that dietary restraint is not a consistent predictor of energy intake and body weight[51
]. In contrast, we found that neuronal activation in response to food cues, specifically in the right DLPFC was negatively correlated with subsequent energy intake. This suggests that food intake may be partially under inhibitory cognitive control and that a more objective measure such as neuronal response is a better predictor of energy intake. We are not aware of any other studies examining such a relationship.
In conclusion, the results of this study demonstrate that there are important sex-based differences in the appetitive responses to food. Women have a much more robust neuronal response to food-related visual cues in prefrontal and parietal cortex than men, suggesting greater cognitive processing related to executive function, such as planning, guidance or evaluation of behavior. Women have a heightened satiety response to meals as compared to men, and men are more likely to overeat during ad libitum feeding. Finally, increased DLPFC response to food cues, perhaps relating to inhibitory cognitive control may be a better predictor of food intake than more subjective behavioral measures. These findings emphasize the importance of considering sex when designing and interpreting feeding-related behavioral and neuroimaging studies and suggest that sex should be considered when behavioral interventions related to food intake are implemented.