The limited data available suggest that exposure to weight-based stigmatization leads to overeating and increased desire for food. In the present study, overweight and obese individuals (BMI from 25-35 kg/m2) who are generally healthy will be randomized to read a weight-stigma article or control article and subsequently scanned to collect fMRI data. These procedures will be employed to accomplish two specific aims.

Specific Aim 1: Determine the neural mechanisms involved in exposure to weight stigma on central control of appetite in overweight and obese individuals. To accomplish this aim we will collect fMRI data in study participants when viewing food and scenery pictures after being exposed to either a weight-stigma or control article. In addition, participants will complete validated questionnaires to measure perceived weight-stigma experiences and social support for eating and physical activity. Hypothesis: After reading an article depicting weight stigmatization, when shown pictures of food in the fMRI scanner, overweight/obese individuals that perceive themselves as having experienced higher levels of weight stigma and lower levels of social support, will have higher activations of brain regions that control appetite and food reward (amygdala, orbitofrontal cortex, striatum, insula) and reduced activations in brain areas that regulate self-control and decision making (prefrontal cortex and cingulate cortex respectively) compared to a control group that reads a non-weight stigma article.

Specific Aim 2: To assess the relationship between activity in appetitive and self-control brain regions and self-reported, eating-related behavior. To accomplish this aim, participants will also complete questionnaires that measure self-reported food intake motivation (dietary restraint, disinhibition and hunger), appetitive responses, and mood. Hypothesis: Higher activations in appetite and reward regions and lower activations in self-control brain regions will be correlated with higher levels of dietary disinhibition, hunger/appetite, and dietary restraint.

Introduction Over two-thirds of Americans are either overweight or obese (Fryar et al., 2016) and thus the search for therapeutic strategies for the overweight/obesity epidemic is key. As much as 20% of overweight/obese individuals also report having weight stigma experiences (Levy and Pilfer, 2012) and may experience stigmatization repeatedly over the course of their lifetimes. Weight stigma, as defined by Araiza and Wellman (Araiza and Wellman, 2017), is the social depreciation and condemnation of individuals with higher body weight.

Emerging data from two recent review articles demonstrate that the negative impact of weight stigma experienced by overweight and obese individuals occurs on the physiological, psychological, and behavioral levels (Vartanian and Porter, 2016; Wu and Berry, 2018). Weight stigma could actually lead to overconsumption of food and eating disorders such as binge eating (Wott and Carels, 2010; Almeida et al., 2011) which can further exacerbate the obesity epidemic. For example, the more participants perceived themselves as experiencing weight stigma, the more calories they selected (Araiza and Wellman, 2017) or consumed (Major et al., 2014) and the more poorly they performed on cognitive tests (Araiza and Wellman, 2017) when they read an article depicting discrimination against individuals with higher body weight compared to a control group. In the Major et al. study, women who perceived themselves as being overweight consumed 80 calories more of a high-calorie snack which translated to a magnitude of effect of 47%. Perceived weight stigma has also been shown to be positively correlated with emotional and rigid restrained eating as well as predicting weight gain over a ten-week period (Wellman et al., 2017).

Importantly, individuals with higher body weights are more affected when put in situations that remind them more of weight stigmatization (Major et al., 2014; Hunger et al., 2015), though not everyone may respond in the same manner. While data exist to show the negative impacts of weight stigma of overweight/obese individuals on eating behavior, there is a paucity of data regarding the effect of exposure to weight-stigma content on the neural control of appetite and self-control in overweight/obese individuals. The so-called 'appetitive network' is centered around the following interconnected brain regions: the amygdala and hippocampus, the orbitofrontal cortex (OFC) and adjacent ventromedial prefrontal cortex (VMPFC), the striatum, and the insula. These areas of the brain are normally activated during functional magnetic resonance imaging (fMRI) studies where food cue reactivity is assessed, and the activity is regulated by peripheral signals of energy balance, current hunger, and personality traits (Dagher, 2012). Furthermore, how these neural control measures correlate with self-reports of weight stigma experiences, social support for eating behavior and physical activity, food intake motivation (dietary restraint, disinhibition and hunger), mood and appetite require further investigation.

Study Design This is a cross-sectional study of overweight/obese, generally healthy subjects. After having completed a telephone prescreening test to determine eligibility for the study, subjects will be invited to the Brain Imaging Center (BIC) at the University of Missouri for a one-time research visit lasting approximately three hours. The subject will report to the BIC in the fasted state. The sequence of events during this test visit is outlined in Figure 1 and is described in detail below.

Upon arrival at the BIC, the subject will be screened for eligibility for MRI research following the standard University of Missouri screening protocol. The subject will then be taken through the informed consent process and then testing will begin. Informed consent is performed in a quiet, closed office and the subject will be given ample time to discuss the study and ask questions. Anthropometric measurements (weight and height), as well as a finger prick glucose measurement, is preformed and subsequently, the subject is asked to fill out a series of questionnaires (appetite/ mood, social support, weight stigma experiences, Three-Factor Eating questionnaire). Research staff are present to answer any questions the subject may have about the surveys. Then, the subject will read their assigned weight-stigma or control article (randomization to either the control or weight stigma article condition will be done before data collection commence). One of the questionnaires (appetite/mood) is repeated after reading the article just prior to scanning, and also again after scanning is over. The subject then undergoes fMRI scanning followed by a final repeat of the appetite/mood survey and a finger stick for glucose measurement. Upon completion of all the test procedures, the subject is debriefed as to the purpose of the article and told that the article was fictional.

Inclusion Criteria:

• Generally healthy individuals aged from 18 to 55 years
• BMI 25-35 kg/m2 will be recruited

Exclusion Criteria:

• Being on a weight-loss or special diet
• Taking any medications or drugs known to affect appetite
• Have serious claustrophobia.
• Individuals with mental disorders (self-report) will be excluded.
• Due to MRI, any individuals with metallic objects in their body, including surgical staples left in the body following surgery, middle ear prosthesis, permanent eye liner, metal foreign objects lodged inside the eye, heart pacemakers, and/or pins inside the knee or other joints or who are pregnant or could be pregnant (assessed through a urine pregnancy test for women) will be excluded from this study because of the risk associated with the MRI scanner.