A recent study published in Nature Metabolism explores the neurophysiological and metabolic impacts of sucralose—a widely consumed non-caloric sweetener—on appetite regulation. Researchers used perfusion arterial spin labeling (pASL) MRI to investigate how sucralose, compared to caloric sucrose and water, alters brain activity in hypothalamic subfields and influences hunger, reward processing, and connectivity in different brain regions.
The study was motivated by the growing public health interest in understanding how non-caloric sweeteners may impact appetite, particularly as their use increases in weight management and sugar-reduction strategies. The authors hypothesized that sucralose might increase hunger more than water, but this was not statistically confirmed. They speculated that the absence of significant hunger differences might be due to a disconnect between the expected caloric intake from a sweet taste and the actual absence of energy content, a mismatch that could influence appetite signals in more complex ways.
A key strength of this study was its fine-grained anatomical focus on two hypothalamic subfields: the lateral hypothalamus, associated with hunger stimulation, and the medial hypothalamus—specifically the ventromedial hypothalamic nucleus (VMH) and the arcuate nucleus—both linked to satiety and nutrient sensing. Consistent with classic rodent studies, the medial hypothalamus showed changes in blood flow that correlated with changes in circulating glucose and reductions in hunger. Sucrose, but not sucralose, produced significant decreases in medial hypothalamic activity, suggesting a stronger nutrient-sensing and satiety response to caloric sugar.
Interestingly, sucralose induced the most notable changes in the lateral hypothalamus. Functional connectivity analyses revealed that sucralose increased coupling between the hypothalamus and brain regions involved in attention, motivation, and sensory processing, such as the anterior cingulate cortex and the superior parietal lobule. These findings suggest that even without caloric content, sucralose may enhance the brain’s appetite-reward signaling network and potentially influence food-seeking behavior.
Weight status appeared to be an important moderator. Among participants with a healthy weight, sucralose—compared to sucrose—heightened connectivity between the hypothalamus and several cortical areas involved in decision-making, memory, and sensory integration. These effects were attenuated or absent in participants with overweight or obesity, hinting at possible desensitization or altered neural sensitivity to non-caloric sweeteners in these populations.
This study contributes to a growing body of evidence suggesting that non-caloric sweeteners like sucralose are not metabolically inert. While they do not suppress hunger in the same way as caloric sugars, they appear to engage reward and motivation pathways and alter hypothalamic activity in a weight-dependent manner. These findings underscore the complexity of appetite regulation and raise important questions about the long-term neural and behavioral consequences of widespread non-caloric sweetener consumption.
Sources: Nature Metabolism
