Obese individuals possess impaired connections between the dorsolateral hippocampus and the lateral hypothalamus, which may impact their ability to control or regulate emotional responses when anticipating rewarding meals or treats, according to new research.
Orexigenic appetitive processing relies on the integration of sensory, interoceptive and hormonal signals to govern consummatory behaviors. Dysregulation of this process leads to maladaptive eating behavior such as binge eating and is associated with obesity. This circuit, however, was elusive in humans — until now. Image credit: Barbosa et al., doi: 10.1038/s41586-023-06459-w.
“Our findings underscore that some individual’s brains can be fundamentally different in regions that increase the risk for obesity,” said Dr. Casey Halpern, a researcher at Penn Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center.
“Conditions like disordered eating and obesity are a lot more complicated than simply managing self-control and eating healthier.”
“What these individuals need is not more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”
The dorsolateral hippocampus is located in the region of the brain that processes memory, and the lateral hypothalamus is in the region of the brain that is responsible for keeping the body in a stable state, called homeostasis.
Previous research has found an association with loss of function in the human hippocampus in individuals with obesity and related disordered eating, like binge eating disorder.
However, outside of imaging techniques such as magnetic resonance imaging (MRI), the role of the hippocampus has been difficult to study in humans with obesity and related eating disorders.
In their new study, Dr. Halpern and colleagues were able to evaluate patients whose brains were already being monitored electrically in the Epilepsy Monitoring Unit.
They monitored brain activity as patients anticipated and then received a sweet treat (a chocolate milkshake).
The authors found that both the dorsolateral hippocampus and the lateral hypothalamus activated simultaneously when participants anticipated receiving the rewarding meal.
Using stimulation techniques, they confirmed that this specific zone of the hippocampus, the dorsolateral hippocampus, and the lateral hypothalamus exhibited extremely strong connectivity, as well.
In individuals with obesity, they found that the impairment of this hypothalamus-hippocampus circuit was directly proportional to their body mass index (BMI). That is, in participants with a high BMI, the connection was even more disturbed.
To further validate the connection, the team used a technique called brain clearing, to analyze brain tissue.
The technique revealed melanin-concentrating hormone, a hormone known to regulate feeding behavior that is produced in the lateral hypothalamus.
The scientists found the presence of the melanin-concentrating hormone in the dorsolateral hippocampus, and nowhere else, confirming a link between the two regions.
“The hippocampus has never been targeted to treat obesity, or the disordered eating that can sometimes cause obesity,” Dr. Halpern said.
“We hope to be able to use this research to both identify which individuals who are likely to develop obesity later in life, and to develop novel therapies — both invasive and not — to help improve function of this critical circuit that seems to go awry in patients who are obese.”
The research is described in a paper in the journal Nature.
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D.A.N. Barbosa et al. An orexigenic subnetwork within the human hippocampus. Nature, published online August 30, 2023; doi: 10.1038/s41586-023-06459-w
