Oxytocin (OXT), shown to decrease food intake in animal models and men, is a promising novel treatment for obesity. We have shown that in men with overweight and obesity, intranasal (IN) OXT reduced the functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent signal in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system, in response to high-calorie food vs. nonfood images. Here, we employed functional connectivity fMRI analysis, which measures the synchrony in activation between neural systems in a context-dependent manner. We hypothesized that OXT would attenuate the functional connectivity of the VTA with key food motivation brain areas only when participants viewed high-calorie food stimuli.
This randomized, double-blind, and placebo-controlled crossover study of 24 IU IN OXT included ten men with overweight or obesity (mean ± SEM BMI: 28.9 ± 0.8 kg/m2). Following drug administration, subjects completed an fMRI food motivation paradigm including images of high and low-calorie foods, nonfood objects, and fixation stimuli. A psychophysiological interaction analysis was performed with the VTA as seed region.
Following OXT administration, compared with placebo, participants exhibited significantly attenuated functional connectivity between the VTA and the insula, oral somatosensory cortex, amygdala, hippocampus, operculum, and middle temporal gyrus in response to viewing high-calorie foods (Z ≥ 3.1, cluster-corrected, p < 0.05). There was no difference in functional connectivity between VTA and these brain areas when comparing OXT and placebo for low-calorie food, nonfood, and fixation images.
In men with overweight and obesity, OXT attenuates the functional connectivity between the VTA and food motivation brain regions in response to high-calorie visual food images. These findings could partially explain the observed anorexigenic effect of OXT, providing insight into the mechanism through which OXT ameliorates food cue-induced reward anticipation in patients with obesity. Additional studies are ongoing to further delineate the anorexigenic effect of OXT in obesity.
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We would like to thank our participants as well as the staff at the Massachusetts General Hospital Harvard Clinical and Translational Science Center and Athinoula A. Martinos Center for Biomedical Imaging.
Conflict of interest
The study was supported by the Boston Nutrition Obesity Research Center—5P30DK046200-20; Nutrition Obesity Research Center at Harvard—P30DK040561; 5R01DK109932-02; K23 MH092560; K24 MH120568; and Harvard Clinical and Translational Science Center 0UL1TR001102-01. EAL has a financial interest in OXT Therapeutics, a company developing an IN OXT and long-acting analogs of OXT to treat obesity and metabolic disease. EAL’s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. This company was not involved in any way in this research. The other authors declare that they have no conflict of interest.
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Kerem, L., Hadjikhani, N., Holsen, L. et al. Oxytocin reduces the functional connectivity between brain regions involved in eating behavior in men with overweight and obesity. Int J Obes 44, 980–989 (2020). https://doi.org/10.1038/s41366-019-0489-7
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