Summary: Researchers identified a reduction in function in the lateral orbitofrontal cortex of obese mice.
Source: University of Calgary
University of Calgary researchers find diet-induced obesity is linked to a functional change in the brain.
A study published in Nature Neuroscience reports that diet-induced obesity in mice is associated with reduced function in a brain region known as the lateral orbitofrontal cortex (lOFC). The lOFC plays a central role in evaluating rewards and deciding whether to act to obtain them. When this “brake” signal is weakened, animals show reduced flexibility in changing their behavior after the value of a food reward drops.
“We all change how we value food,” says Dr. Stephanie Borgland, PhD, professor at the Cumming School of Medicine and senior author on the study. “For example, when you’re hungry, a chocolate bar is high value. If you were forced to eat five or six chocolate bars, however, you would become averse to it. This process is called devaluation.”
Until now, researchers knew the brain was integral to controlling decisions about eating, but the specific brain circuits that change as obesity develops were not fully defined. Using mouse models, the Borgland lab adapted three established devaluation methods to examine goal-directed behavior and how it shifts with diet-induced obesity.
Lead investigator Dr. Lauren Seabrook, PhD candidate, explains their key experimental findings. “When we suppressed the brake signal in the lOFC of lean mice, those mice continued to work for sucrose even after they had consumed enough to be fully sated. In contrast, restoring normal activity in the orbitofrontal cortex of obese mice returned their ability to devalue sucrose and regain control over eating-related actions.”
At the cellular level, the study reports that obesity is associated with reduced inhibitory drive in the lOFC. The team used chemogenetic approaches to reduce GABAergic neurotransmission in this region and observed obesity-like impairments in goal-directed behavior. Conversely, pharmacological or optogenetic restoration of inhibitory signaling in the lOFC reinstated behavioral flexibility in obese mice. These interventions demonstrate a causal role for altered inhibition within the lOFC in the shift from flexible to more habitual, food-seeking behavior in an obesogenic condition.
The implications of these findings are broad. Diet-induced obesity and the metabolic diseases that often accompany it are major public health concerns. In Canada, approximately one in four adults (26.6 percent) are currently living with obesity. Obesity increases risk for conditions such as type 2 diabetes, stroke, certain cancers and depression, highlighting the need to understand underlying biological drivers of overeating and weight gain.
“Our research is confirming that overeating is not simply a matter of personal responsibility,” says Dr. Borgland. “Instead, it reflects measurable changes in how the brain processes rewards in response to the food environment. That should shift the conversation away from stigma and toward understanding the biological factors that influence eating behaviour.”
The authors note the importance of reducing stigma around obesity. “You would never stigmatize someone for brain changes due to Multiple Sclerosis or Parkinson’s disease,” a member of the team observes. “Yet people with obesity often face blame even though similar neural changes are involved.”
Following these animal findings, the research team is conducting a pilot study to investigate whether similar orbitofrontal cortex changes occur in humans. Those interested in learning more about the human study can contact the research team by email or phone.
Contributions to the study include Lauren Seabrook, PhD’22, and Lindsay Naef, PhD, who contributed equally as co-authors. The study advances understanding of how obesity alters brain circuits that govern decision-making and highlights the lateral orbitofrontal cortex as a critical node in the control of food-seeking behavior.
About this obesity and neuroscience research news
Author: Kyle Marr
Source: University of Calgary
Contact: Kyle Marr – University of Calgary
Image: The image is in the public domain
Original Research: Closed access. “Disinhibition of the orbitofrontal cortex biases decision-making in obesity” by Stephanie Borgland et al., published in Nature Neuroscience.
Abstract
Disinhibition of the orbitofrontal cortex biases decision-making in obesity
The lateral orbitofrontal cortex (lOFC) receives sensory information about food and integrates these signals with expected outcomes to guide future actions, and thus may play a key role in a distributed network of neural circuits that regulate feeding behavior.
Here, we reveal a new role for the lOFC in the cognitive control of behavior in obesity. Food-seeking behavior is biased in obesity such that in male obese mice, behaviors are less flexible to changes in the perceived value of the outcome.
Obesity is associated with reduced lOFC inhibitory drive and chemogenetic reduction in GABAergic neurotransmission in the lOFC induces obesity-like impairments in goal-directed behavior. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible behavior.
Our results indicate that obesity-induced disinhibition of the lOFC leads to a failure to update changes in the value of food with satiety, which in turn may influence how individuals make decisions in an obesogenic environment.