Sweet taste is a strong stimulative factor influencing appetitive responses. Sweet taste stimulation can trigger the release of dopamine, serotonin, and endorphins (Melchior et al., 1991; Yamamoto et al., 2000; Hajnal et al., 2004; Huang et al., 2005; Hajnal et al., 2009; Roitman et al., 2010; Oliveira-Maia et al., 2011), then produce happiness and analgesic effects in mammals (Calcagnetti and Holtzman, 1992; Blass and Shah, 1995; Blass and Watt, 1999; Carbajal et al., 1999; Wahl et al., 2017). Sweet taste is involved in nutrient sensing, energy stores, and triggering metabolic and behavioral responses to maintain energy balance. Importantly, the alteration in sucrose taste sensitivity is associated with obesity and type 2 diabetes mellitus (Hajnal et al., 2005; Pasquet et al., 2007; Gondivkar et al., 2009; Pepino et al., 2010; Sartor et al., 2011; Berthoud and Zheng, 2012; Skrandies and Zschieschang, 2015; Hardikar et al., 2017; May et al., 2019). In addition, the underlying mechanisms of gustatory reward are conserved from invertebrates to mammals (Burke et al., 2012).

Sucrose taste perception is largely influenced by genetics, but also can be modulated by external nutritional conditions (Bachmanov et al., 2011; Hwang et al., 2019). The effect of diet composition on sucrose taste is of particular interest and has drawn considerable attention. In humans, studies have revealed a negative correlation between the levels of dietary sugar and sweet taste perception (Sartor et al., 2011; Bartolotto, 2015; Wise et al., 2016). Much progress has been made in the physiology and molecular biology of taste in Drosophila (Ishimoto and Tanimura, 2004), and sucrose taste sensitivity has been reported to be affected by various diets (Wang et al., 2016; Wang et al., 2020; May and Dus, 2021). The high-sugar diets attenuated the responses of gustatory neurons to sweet taste stimuli, leading to higher food intake and fat accumulation (May et al., 2019; Vaziri et al., 2020). Similarly, in rodents, the rats fed with a high-sugar diet, or a high-fat, high-sugar diet, displayed a lower taste response to sucrose (Weiss et al., 2019; McCluskey et al., 2020). However, unlike dietary carbohydrates, the effect of dietary protein on sucrose taste is controversial. One earlier study revealed that sweet taste response to sucrose was enhanced after protein-only food in locusts (Simpson et al., 1991), while another study demonstrated that low protein diets increased sweet taste sensitivity in fruit flies (Wang et al., 2020). Currently, there is no consensus on the effect of dietary macronutrients on the regulation of sucrose taste sensation. Since most studies evaluated carbohydrates or protein separately (Wise et al., 2016; Jayasinghe et al., 2017; May et al., 2019; McCluskey et al., 2020), there was no consideration of the interaction between protein and carbohydrates on sweet taste sensation.

The nutritional geometry framework (NGF) is to explore how the outcomes of fitness and disease are associated with the interaction of macronutrients in different organisms and to define nutritional interventions for the physiological, disease, and life-history traits. (Lee et al., 2008; Solon-Biet et al., 2014; Simpson et al., 2015; Le Couteur et al., 2016; Raubenheimer and Simpson, 2016; Silva-Soares et al., 2017; Simpson et al., 2017; Semaniuk et al., 2018; Simpson et al., 2018; Hew et al., 2020). The NGF defines nutrition as a multidimensional space in which the micronutrients are delineated by separate axes. Variables of phenotypic features are superimposed on nutritional space by plotting response surfaces (Solon-Biet et al., 2014). In this study, we first applied NGF to investigate how the balance of macronutrients affects sucrose taste sensation and to identify dietary protein and carbohydrate intakes that maximize sweet taste sensitivity to sucrose in Drosophila. In our response surf-aces, isolines represent areas of equality for the variable, and red areas indicate the highest response value of the variable, while dark blue areas indicate the lowest response value. We demonstrate that sucrose taste sensitivity is affected by the balance of dietary protein and carbohydrates and that high protein combined with low carbohydrates enhances sucrose taste sensitivity.