Novel insights into weight gain

Disrupted connections between memory and appetite regulating brain circuits are directly proportional to body mass index (BMI), notably in patients who suffer from disordered or overeating that can lead to obesity, such as binge eating disorder (BED), according to new research from the Perelman School of Medicine at the University of Pennsylvania. The research notes that individuals who are obese have impaired connections between the dorsolateral hippocampus (dlHPC) and the lateral hypothalamus (LH), which may impact their ability to control or regulate emotional responses when anticipating rewarding meals or treats.

Researchers monitored brain activity as patients anticipated and then received a sweet treat (a chocolate milkshake). They found that both the dlHPC and the LH activated simultaneously when participants anticipated receiving the rewarding meal. These researchers confirmed using stimulation techniques that this specific zone of the hippocampus, the dlHPC, and LH exhibited extremely strong connectivity, as well.

In individuals with obesity, researchers found that the impairment of this hypothalamus-hippocampus circuit was directly proportional to their BMI. That is, in participants with a high BMI, the connection was even more disturbed.

To further validate the connection, Halpern's 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 LH. They found the presence of MCH in the dlHPC, and nowhere else, confirming a link between the two regions.

Reference: Daniel A. N. Barbosa, Sandra Gattas, Juliana S. Salgado, Fiene Marie Kuijper, Allan R. Wang, Yuhao Huang, Bina Kakusa, Christoph Leuze, Artur Luczak, Paul Rapp, Robert C. Malenka, Dora Hermes, Kai J. Miller, Boris D. Heifets, Cara Bohon, Jennifer A. McNab, Casey H. Halpern. An orexigenic subnetwork within the human hippocampus. Nature, 2023; DOI: 10.1038/s41586-023-06459-w