The prevalence of Class III obesity (BMI ≥ 40 kg/m²) and endometrial cancer (EC) is rising, with severe obesity increasing mortality risk for both conditions. While prior research has explored the neural response to food cues in obesity, no studies have examined this by obesity class in cancer survivors. This study aimed to evaluate the neural response to visual food cues in obese (BMI ≥ 30 kg/m²) Stage I EC survivors seeking weight loss, stratified by obesity class (I/II and III). The researchers hypothesized that women with Class III obesity would show greater activation in brain regions associated with food reward and motivation in response to high-calorie images, even after eating, compared to Class I/II individuals. Understanding these neural differences is crucial for developing tailored behavioral weight loss interventions.

Existing literature demonstrates a link between obesity and disrupted neurological reward systems, leading to overeating of high-calorie foods. Studies in obese individuals without cancer have shown increased activation in regions like the dorsal striatum (reward anticipation), insula (taste processing), and OFC (motivation) in response to high-calorie food stimuli. However, information on neural responses in severely obese adults, especially in comparison with other obesity classes, is limited. Previous studies after bariatric surgery suggest differences in brain activity patterns between severely obese adults and those post-surgery or with normal weight. Prior work by the authors in a smaller sample of endometrial cancer survivors with Class II obesity indicated increased activation in the DLPFC, OFC, and MFG in the pre-meal state and increased activation in the thalamus, posterior cingulate, and precuneus in the post-meal state, alongside unexpected decreased anterior cingulate activation. This study aimed to expand upon this pilot work with a larger sample stratified by obesity class.

Eighty-five obese Stage I endometrial cancer survivors enrolled in a lifestyle intervention participated. Participants underwent fMRI scans in a fasted (pre-meal) and fed (post-meal) state. A standardized 1000 kcal meal was provided, and food consumption was measured. A visual food cue task was implemented, presenting high-calorie, low-calorie, and non-food images side-by-side, with participants indicating whether they were 'same' or 'different'. BrainVoyager 20.2 was used for fMRI data analysis. Preprocessing involved motion correction, spatial smoothing, and high-pass filtering. A random-effects general linear model analysis compared high-calorie vs. non-food contrasts. Whole brain cluster-based threshold correction was applied to control for multiple comparisons (p < 0.05). Secondary analyses included extracting the mean β-values for significant regions and performing one-way ANOVAs to compare between obesity groups. Correlations between brain activation, food preferences, and meal consumption variables were also explored.

In the fasted state, increased activation was observed in the OFC and DLPFC across both obesity groups, with significantly higher DLPFC activation in Class III compared to Class I/II (p = 0.04). Unexpectedly, insula activation was significantly lower in Class I/II compared to Class III (p = 0.03). In the fed state, increased DLPFC activation persisted in both groups, without a significant difference between obesity classes. Post-meal, higher DLPFC activation in both Class III and Class I/II was positively correlated with carbohydrate intake. In Class III individuals, higher DLPFC activation was also inversely correlated with fat intake and fruit/vegetable liking scores. Other regions, including the precuneus and precentral gyrus showed increased activity primarily in the Class III group in either the fasted or fed state. Conversely, decreased activation in regions like the posterior cingulate and insula were observed in the Class I/II group in the fasted state.

The study's findings support prior research showing increased DLPFC activation in obese individuals, linking it to cognitive control and inhibitory processes. The significantly higher DLPFC activation in Class III obese individuals suggests that this region's role in managing food cravings and impulses might be particularly pronounced in severe obesity. The unexpected decreased insula activation in the Class I/II group requires further investigation but may indicate differences in taste perception or reward processing between obesity classes. The correlations observed between DLPFC activation and dietary components highlight the complexity of the relationship between brain activity and eating behavior. The findings suggest that attention training or DLPFC-targeted neuromodulation could be beneficial components of weight loss interventions, particularly for severely obese individuals.

This study provides novel insights into the neural responses to food cues across different obesity classes in endometrial cancer survivors. The enhanced DLPFC activation in Class III obesity underscores the potential of targeting this brain region in weight loss interventions. Future research should explore the insula's role in this context and investigate the generalizability of these findings to non-cancer populations and other obesity-related diseases. Further research should also investigate other brain regions like the precuneus and precentral gyrus to understand their role in the response to food cues.

The study's limitations include the use of only endometrial cancer survivors, which might limit the generalizability of findings. The lack of a non-cancer control group with comparable obesity classes makes direct comparisons difficult. As with many neuroimaging studies, limitations related to sample size and study design might influence the reproducibility and interpretation of findings. Finally, the cross-sectional design only offers a snapshot of the neural responses, preventing inferences about causality.