Highlights d Consumption of sucralose combined with carbohydrates impairs insulin sensitivity d This metabolic impairment is associated with decreases in neural responses to sugar d However, sweet taste perception is unaltered d Insulin sensitivity is not altered by sucralose or carbohydrate consumption alone

Summary Post-ingestive signals related to nutrient metabolism are thought to be the primary drivers of reinforcement potency of energy sources. Here, in a series of neuroimaging and indirect calorimetry human studies, we examine the relative roles of caloric load and perceived sweetness in driving metabolic, perceptual and brain responses to sugared beverages. Whereas caloric load was manipulated using the tasteless carbohydrate maltodextrin, sweetness levels were manipulated using the non-nutritive sweetener sucralose. By formulating beverages that contain different amounts of maltodextrin+sucralose, we demonstrate a non-linear association between caloric load, metabolic response and reinforcement potency, which is driven in part by the extent to which sweetness is proportional to caloric load. In particular, we show that (1) lower calorie beverages can produce greater metabolic response and condition greater brain response and liking than higher calorie beverages and (2) when sweetness is proportional to caloric load greater metabolic responses are observed. These results demonstrate a non-linear association between caloric load and reward and describe an unanticipated role for sweet taste in regulating carbohydrate metabolism, revealing a novel mechanism by which sugar-sweetened beverages influence physiological responses to carbohydrate ingestion.