Oxytocin Has Dramatic Effect on Brains of Obese People Viewing Tasty Food

Obesity’s effects on the body are well known, but its effects on the brain are just as powerful. The way that obesity warps the mind’s perceptions of food is so strong that some researchers are arguing that we should treat it by bypassing the body and going straight to the brain. In a presentation at the Endocrine Society’s annual meeting on Monday, they revealed that they’ve found the brain molecule that can do the job.

In her presentation in New Orleans, Dr. Liya Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, debuted her research showing that the way the brain reacts to high-calorie food can be shifted by oxytocin, a hormone. Oxytocin is sometimes known as the “love hormone,” released when you hug your dog or spend quality time with your significant other. Kerem’s evidence suggests that it could also be a viable treatment for obesity in the future.

Her work shows that the brains of obese people who took a dose of oxytocin before looking at images of high-calorie food responded to the photos differently. The reward center of the brain, which is normally highly activated when obese people look at food, was a lot calmer than expected.

“Studies consistently show that in the state of obesity, there is hyper-activation of reward-related brain circuitry in response to viewing pictures of palatable food,” Kerem said at the conference. “So this hyper-activation in food-related brain areas might represent a therapeutic target. Oxytocin might be one of the therapeutic agents.”

The work Kerem presented at the conference hasn’t been published in a journal yet, and she notes that one of her co-authors had previously worked as a consultant at OXT Therpeutics, a company that conducted earlier work on oxytocin’s effects on obesity.

Kerem’s work is based on brain imaging from a study published in Neuropsychopharmacology in February 2018, led by Franziska Plessow, Ph.D., a neuroendocrinologist also at Massachusetts General Hospital. In that study, 10 obese individuals received doses of oxytocin or placebos, and then viewed images of high-calorie foods, low-calorie foods, random objects, or blurred images.

The study revealed that oxytocin reduced bloodflow to the ventral tegmenal area of the brain when patients viewed high-calorie, but not low-calorie, food images This area, Kerem explains, is involved in the pursuit of desirable food. It forms the central hub of the brain’s reward center — a circuit that floods with feel-good neurotransmitters like dopamine when appropriately stimulated.

Kerem’s analysis builds on the previous work by showing that the effects of oxytocin go far beyond a single brain area. She looked into the brain’s patterns of functional connectivity — the dialogue between different brain regions that happens when a person performs a task.

"Targeting the hyper-activation of reward areas with oxytocin may inhibit overeating behavior.

Oxytocin, she found, affects an entire network of food-related reward circuitry in the brains of obese individuals. A dose of the hormone revealed less functional connectivity between “key food motivation areas” that control cognitive and emotional processing related to food, she notes. These areas include the insula, parietal operculum, amygdala, anterior and posterior cingulate, and hippocampus.

These regions become hyperactive when obese individuals see food-related images, but the new work shows that the presence of oxytocin can help calm things down. Even more importantly, this reduction in activity only happened in response to the images of high-calorie food, making oxytocin an even stronger contender for obesity treatment.

“Since we know that overconsumption of high calorie foods is a major contributor to obesity, targeting the hyper-activation of reward areas with oxytocin may inhibit overeating behavior,” Kerem says.

This study didn’t go beyond identifying that relationship and linking oxytocin to weight loss, but more studies beyond the small pilot study showing oxytocin’s importance in 2013 are currently taking place, says Kerem.

Partial Abstract:

Methods: In this randomized, double-blind, placebo-controlled crossover study of 24 IU IN OXT, 10 overweight/obese (mean±SD BMI 28.9±0.8 kg/m2), otherwise healthy men age 31.4±1.8 years presented after a 10-h overnight fast. Sixty min after drug administration, subjects started an established fMRI food motivation paradigm that included images of high and low-calorie foods, household objects, and fixation stimuli. Using psychophysiological interaction analysis, the VTA was anatomically defined as the seed region to explore effects of OXT on functional connectivity.

Results:Following OXT administration, compared to placebo, participants showed significant attenuation of the functional connectivity between the VTA and insula, parietal operculum, amygdala, anterior and posterior cingulate, and hippocampus in response to viewing high-calorie food stimuli vs. objects (Z≥3.1, cluster corrected, P=0.05).

Conclusions:Here we have shown in overweight/obese men that OXT attenuates functional connectivity between the VTA and brain regions associated with the cognitive, sensory and emotional processing of food images. This is particularly relevant to obese individuals, since previous studies have shown greater activation to palatable food images in these areas (e.g., amygdala, hippocampus and insula), and it has been proposed that this hyperactivity of the dopaminergic reward circuit renders obese individuals prone to overeating. Attenuated functional connectivity findings reported here could partially explain the clinically-observed anorexigenic effect of OXT, providing insight into the mechanism through which OXT ameliorates food-cue-induced, CNS-mediated reward anticipation in obese patients. Additional studies are ongoing to further delineate the neural connections underlying the anorexigenic effect of OXT in human obesity.