Obesity hinders brain recognition of nutrient signals

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Recent research has demonstrated 1 that obesity impairs the mechanisms that allow our brains to realize when our stomachs are full and that these changes are maintained despite dieting, giving insights into why it is difficult for obese people to avoid excessive eating and why there is often a yo-yo effect after dieting.

It has been long known that a failure to appropriately respond to satiety signals is related to obesity and disordered eating. In this new study, a multinational team directly and randomly delivered water (as control), fat or glucose (sugar) to the stomachs of 28 people considered lean, with a body mass index (BMI) ≤ 25, and 30 individuals with medical obesity and a BMI ≥ 30. Right after, the participants were placed in a fMRI (functional magnetic resonance imaging) machine and their brain activity was quantified. Interestingly, lean participants showed lower activity in various brain regions after glucose or fat infusions, but this was not the case for obese participants, for whom the brain did not register any changes. This indicated that obesity hinders nutrient recognition by the brain.

Then, the researchers used using single photon emission computed tomography (SPECT) to investigate the activity of the striatum, a brain region related to food seeking and eating behaviour, and whose activity is related to release of the neurotransmitter dopamine –the same one involved in pleasurable sensation, but in another brain region–. Interestingly, although both glucose and fat decreased the activity of the striatum in lean people; only glucose, but not fat, did cause changes in the striatum in obese participants. In addition, these changes were of a smaller scale than those observed in lean people.

Finally, the obese participants underwent a 12-week weight loss program. Those who achieved a 10% weight reduction were subjected again to the previous testing. Despite their weight loss, their brains did not register any changes in response to fat or glucose infusion to their stomachs. This indicated that obesity hinders nutrient recognition by the brain and this effect remains despite losing weight or changing eating habits.

This research is interesting in that it provides an explanation to the common observation why obese people cannot seem to get their eating under control. It is not lack of will, but that their brains cannot sense the content in their stomachs. However, it is still early days to consider this information of use for practical, clinical applications, as the underlying mechanisms remain unknown and the duration/extent of effects is also unclear. In addition, it would be interesting to see if there’d be a relationship to the microbiome and the brain-gut-axis. I will stay abreast of new developments as this is certainly an interesting field of research, given the millions of people worldwide affected by obesity.


  1. van Galen, K.A., Schrantee, A., ter Horst, K.W. et al. (2023) Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study. Nat Metab doi: 10.1038/s42255-023-00816-9

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