Sweet taste perception is a crucial evolutionary adaptation that allows organisms to recognize the nutritional value of food. This sensory cue provides a rewarding signal that strongly stimulates appetite and food intake. However, due to the preference for sweetness, overconsumption of sweetened foods and beverages has been considered as the main cause of the rising prevalence of obesity in humans. As such, understanding the neural mechanisms that underlie the effects of sweet taste perception on feeding behaviour is of critical importance for developing effective strategies to mitigate the negative health consequences associated with excessive sugar intake.

Non-nutritive sweeteners (NNSs), commonly used as a substitute for sugar in a large variety of foods and beverages due to their low-calorie or no-calorie content, are being consumed by billions of individuals globally. The primary function of NNSs is to provide a sweet taste sensation without adding calories of sugar, thereby enhancing the palatability of low-carbohydrate foods or beverages. Sweetness detection is mediated by taste receptors located in the taste buds on the tongue. These receptors activate sensory neurons, which transmit the sweet signal to higher-order neurons in specific regions of the brain responsible for generating sweet taste perception, such as the nucleus of the solitary tract, parabrachial nucleus, thalamus, and insula (Yarmolinsky et al., 2009). Previous studies have shown that the neural circuitry involved in sweet taste information processing is complex and includes multiple neurons (Dahanukar et al., 2007; Fujii et al., 2015; Jiao et al., 2007; Jiao et al., 2008; Kain and Dahanukar, 2015; Slone et al., 2007; Thoma et al., 2016). Moreover, we have shown previously that chronic NNS consumption requires a complex neural signalling to induce a fasting response in the brain (Wang et al., 2016). However, humans use NNSs to increase the palatability, and much less is known about how NNSs impact feeding.

Drosophila is an excellent model organism for investigating the effects of sweet taste perception on food intake. Its taste organ system is similar to that of mammals (Staats et al., 2018), and sweet taste perception strongly influences its feeding behaviour (May et al., 2020; May et al., 2019). Furthermore, NNSs have been shown to elicit a sweet taste perception in Drosophila (LeDue et al., 2015; Wang et al., 2016; Wang et al., 2017). Therefore, in this study, we investigated the mechanisms underlying how the NNSs sucralose can impact acute food intake, and then dissected the underlying neural pathways that control this effect. We find that the NNSs sucralose shows a potent ability to increase food intake, and this effect is mediated by sweet taste neurons, and octopamine, dopamine, and NPF systems.