Brain Sex Differences in Obesity

With the increasing prevalence, concern, and discussion of obesity in the United States, researchers have been working to tackle the following questions: What are the underpinnings of obesity, and how does it vary amongst groups of people, specifically between males and females? Distinguishable brain features amongst obese versus non-obese people have been analyzed, so the next step is to dive deeper into variables such as sex. Through scientific exploration and discovery, we can get closer to depicting the unique presentations of obesity and incentivizing practicable personalized treatment and prevention plans.

In 2023, the NIH published a study by Bhatt et al. titled “Integrated multi-modal brain signatures predict sex-specific obesity status.” In this paper, the team compared the brain properties and clinical information of four groups of participants: males and females, either with a BMI greater than 25 (overweight or obese) or between 19-20 (non-overweight). Multi-modal MRI data of the brain’s structural and functional characteristics was used to interpret how it computes motivational responses to stimuli such as stress and the environment. The first component of complementary brain imaging measured the morphometric structure of the brain, such as size and shape. Next, they recorded the activity levels of brain regions at resting state, meaning what our brains are up to in the absence of stimuli.

Finally, the white matter connections of the brain were assessed through its diffusion rates. White matter refers to the myelinated axons of neurons, which are analogous to the covered wire along a cord. When a neuron senses something, whether a signal from another neuron or a stimulus from our surroundings, it may get excited enough to trigger an action potential that runs along its axon, releasing a message to relay what it has seen. Therefore, the greater white matter connectivity, the more communication from sensory to processing areas. Yet, in obese participants, the white matter connectivity necessary to modulate the body’s desire for food intake is diminished.

Past experiences and present lifestyle influence sectors of our health. Hence, participants responded to clinical surveys about their moods, behaviors, psychological, familial, and medical history. Questionnaires included food addiction, anxiety, depression, stress, and trauma ratings. Early life adversity was of interest to the researchers. As we grow up, what we go through undoubtedly sways our physical and personal development. Associated areas involved in cognitive control and salience, such as the orbital frontal cortex and interior insula, may be harmed by early life adversity.

After combining clinical and neuroimaging data, a model was developed to detect the presence and magnitude of correlations between variables. From there, experimenters were interested in whether the model could successfully predict if a participant is obese or not without using BMI. Furthermore, they tested if the model could make an accurate read on the sex of an obese participant using correlation clues. By integrating the qualities of a participant, the model accurately guessed if they were obese 77% of the time. From obese participants, the model had a 75% accuracy in determining sex. These results demonstrate just how discernable sex characteristics of the brain can be, especially when it comes to the topic of obesity.

At the end of the study, Bhatt et al. discovered structural and connectivity differences in the brains of overweight and obese participants compared to those who were non-obese. One distinction includes a higher volume of the CSF-producing choroid plexus, which is also a finding in patients with cognitive impairment and even neural degeneration, such as those with Alzheimer’s Disease. Connective differences within circuitry involving the cortex, basal ganglia, and thalamus existed too. Such alterations may affect the organization and regulation of our thoughts, emotions, and actions. Within the basal ganglia lies the putamen, a habit and goal-controlling structure linked to the substantia nigra, a dopamine-producing center. The nucleus accumbens is also a group of nuclei within the basal ganglia, connected to dopamine pathways, the hippocampus, and the amygdala, making the nucleus accumbens a critical structure for handling negative experiences and molding our responses. Altered functionality of the nucleus accumbens is associated with food addiction and emotional disorders.

Furthermore, Dr. Arpana Gupta led a study in which people with high BMIs had boosted dopaminergic reward centers, yet there were sex differences. Men had more connections within the putamen reward center and the posterior insula, which receives somatosensory and motor information. The brains of obese women had higher connectivity in the nucleus accumbens pathway and in the anterior cingulate cortex, which guides what we pay attention to and keeps track of the rewarding nature of how we respond to different events.

In women, the brain’s reward pathways are powerfully directed to seek comfort and pleasure through the ingestion of processed and highly caloric food. Connectivity and signaling in the brain during times of stress motivate women to a degree to ‘eat their feelings away,’ a coping cliché that research suggests holding some weight. Therefore, this robust emotional force drives food cravings, consequentially shaping eating patterns. Circling back to early life adversity and distress, this factors deeply into the machinery of disordered, emotional-based eating.

For men, on the other hand, the eating behaviors that lead to obesity tend to derive from hormonal signaling and digestive sensation irregularities. We all have hormones communicating satiety, such as leptin, and hunger and food-seeking efforts, such as ghrelin. When these transmissions go awry, the brain centers responsible for maintaining energy balance, adequate food intake, and consummatory behavior will also get thrown off, provoking overeating.

With this said, neural plasticity is our not-so-secret weapon that really has a high potential to reverse the damaging effects triggered by the brain’s synaptic connections. With exercises, medication, therapy, or a combination of treatments, the brain can ‘re-wire’ to accelerate healthy functions and habits.