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Journal of Food Science and Technology logoLink to Journal of Food Science and Technology
. 2020 Aug 19;58(6):2227–2236. doi: 10.1007/s13197-020-04733-7

Effect of short-term intake of four sweeteners on feed intake, solution consumption and neurotransmitters release on mice

Jing-Nan Ren 1,#, Kai-Jing Yin 1,#, Gang Fan 1,✉, Xiao Li 1, Lei Zhao 2, Zhi Li 1, Lu-Lu Zhang 1, Ding-Yuan Xie 1, Fang Yuan 1, Si-Yi Pan 1
PMCID: PMC8076381  PMID: 33967319

Abstract

This study focused on the effect of short-term intake of sweeteners on feed intake, solution consumption and neurotransmitters release on mice. The results showed that the free drinking of 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution for 32 days will not affect the normal development of the body weight and feed intake of the mice. The consumption of maltose solution was significantly higher than that of the other sweeteners. The leptin and insulin levels increased significantly after the short-term intake of these four sweeteners. The dopamine (DA) content in the whole brain of the mice increased significantly only in the maltose group. These results indicate that the short-term intake of the preferred concentrations of maltose, stevioside, sucralose and saccharin will not affect the body weight and feed intake of the mice. Mice prefer maltose solution to other sweeteners solutions. The 100 mM maltose solution and 3 mM saccharin solution could result in the oxidative stress on mice after 32 days’ short-term intake. Compared with other sweeteners, only sugars that could be broken down into small molecules of glucose might have a positive effect on dopamine levels.

Keywords: Natural sweeteners, Artificial sweeteners, Short-term intake, Mice, Monoamine neurotransmitters

Introduction

It is reported that increased food intake could result in the increase in obesity levels than reduced energy expenditure (Hall 2017). Because sucrose is easy to cause obesity, impair insulin sensitivity and increase liver size in mice (Togo et al. 2019), the consumption of substituting sugar has increased in recent years for the controlling of body weight and blood glucose. Sweeteners are food additives which can provide sweetness to food and drinks and provide a sweet taste effect like sucrose (Suez et al. 2014). Sweeteners can be divided into natural sweeteners and artificial sweeteners, and they can also be classified into nutritive sweeteners and non-nutritive sweeteners. The nutritive sweeteners have an energy intake similar to sugar, and the non-nutritive sweeteners do not provide energy to body (Jain and Grover 2015). Although sweeteners are not toxic to health, they can result in the increase of appetite, and the modification of immune function, and the secretion of hormones in the GALT (Rosales-Gómez et al. 2018).

Maltose is a disaccharide obtained by hydrolysis of starch, glycogen, dextrin and other macromolecular polysaccharides catalyzed by β-amylase and maltase. Because maltose cannot be used by microorganisms, it can be used as a sweetener to prevent dental caries (Luo et al. 2011). Stevioside is a natural sweetener extracted from the leaves of stevia. It has a very high level of sweetness which is about 250–300 times to that of sucrose (Debnath 2008). The sensory and functional properties of stevioside are superior to many other highly effective sweeteners, and it may become the main source of natural sweetness in the food market. At present, stevia products have been sold as natural and low-calorie sweeteners and have been used in beverage production (Carakostas et al. 2008). It is found that stevioside has lots of beneficial effects in animal models. While Park et al. (2019) found that although rebaudioside-A was a natural sweetener, it had lower detrimental biological impact on hypothalamic cells.

It is considered that the non-nutritive sweeteners are metabolically inactive or inert, while the physiological effects of these sweeteners have been found that they could alter glucose metabolism and stimulate appetite (Nakagawa et al. 2009). Sucralose is a non-nutritive sweetener. Unlike other artificial sweeteners, it is derived from sucrose and is similar in structure to sucrose, and has a very similar taste to sucrose. The sweetness of sucralose is about 600 times to that of sucrose and it is a safe sugar substitute for diabetic patients (Grotz et al. 2003). Saccharin is a low-calorie artificial sweetener. It is generally regarded as an effective sweetener to replace the sweet taste of sucrose, but it cannot replace the taste of sucrose. Some researchers claimed that even the most preferred concentration of saccharin in rats was only as attractive as low concentrations of sucrose (Smith and Sclafani 2002). It is reported that the rat’s perception of sucralose is essentially similar to that of saccharin that the higher concentrations of these two sweeteners will result in the reduced preference or increased aversion (Dess 1993). Erbas et al. (2018) found that long-term consumption of sucralose and saccharin might have harmful effects on cognition and hippocampal integrity in rats. Some in vitro and in vivo studies have found that the exposure to saccharin or sucralose might have harmful effects on various cell types and tissues (Saucedo-Vence et al. 2017).

Maltose, stevioside, sucralose and saccharin are widely used as sweeteners in food industry. While the effect of short-term intake of these four sweeteners on feed intake, solution consumption and neurotransmitters release on mice has seldom been reported. Therefore, this study focused on the effect of short-term intake of natural sweeteners (maltose, stevioside) and artificial sweeteners (sucralose, saccharin) on feed intake, solution consumption and neurotransmitters release on mice. The body weight, feed intake, solution consumption, serum antioxidant indexes (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX)), leptin, insulin and neurotransmitter release on mice were determined after 32 days’ intake of these sweeteners.

Materials and methods

Animals

Three-week-old male (n = 50, body weight 16 ± 2 g) Kunming mice were selected and raised in the Specific Pathogen Free (SPF) animal room of the Experimental Animal Center of Huazhong Agricultural University. The temperature of the animal room was maintained at 24–26 °C, and the relative humidity was 60%. The mice were kept for a 12-h light/dark cycle (lighting time 8:00–20:00). Five mice were placed in a cage, and they had ad libitum access to standard pellet diet (Wuhan Wanqian Jiaxing Bio-Technology Co., Ltd., Wuhan, China) and water. The sterilized sawdust was replaced every 3 days. This study was performed according to the regulation of the administration of affairs concerning experimental animals of P.R. China, and it was confirmed by the Laboratory Animal Research Center of Hubei province and the ethics committee of Huazhong Agricultural University (HZAUMO-2018-030). The mice were pre-adapted for 3 days in the SPF animal room before the experiment.

Materials

Sucralose, maltose and saccharin were purchased from Shanghai Yuanye Biological Co., Ltd (Shanghai, China). Stevioside was purchased from Zhucheng Haotian Pharmaceutical Co., Ltd (Zhucheng, China). Neutral red, malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) assay kit, glutathione peroxidase (GSH-PX) assay kit, leptin assay kit, insulin assay kit, dopamine (DA) assay kit, 5-hydroxytryptamine (5-HT) assay kit, norepinephrine (NE) assay kit and epinephrine (EPI) assay kit were purchased from Shanghai Youxuan Biological Co., Ltd (Shanghai, China).

Effect of short-term intake of the four sweeteners on body weight, feed intake, and solution consumption on mice

The 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution were prepared according to our previous study, and the concentrations of these solutions are the preferred concentrations on mice (Yin et al. 2020). The prepared solutions were sealed and sterilized by a high-pressure steam sterilizer (Shanghai Shenan Medical Instrument Factory, Shanghai, China). Then they were cooled to room temperature.

The 50 male mice were randomly divided into five groups respectively, including the control group, sucralose group, maltose group, saccharin group and stevioside group. Each group contained 2 cages of mice, and five mice were placed in a cage. The treatments of the five groups were conducted as follows: the control group, free drinking water; sucralose group, free drinking 10 mM sucralose solution; maltose group, free drinking 100 mM maltose solution; saccharin group, free drinking 3 mM saccharin solution; stevioside group, free drinking 3 g/L stevioside solution. After 32 days’ feeding, the mice were starved for 12 h. The amount of the remaining feed was weighed every 2 days in order to calculate the feed intake of the mice within 2 days, and the amount of the solutions and the body weight were recorded at a fixed time.

Determination of serum antioxidant indexes, and the content of leptin and insulin in serum of mice

After 32 days’ feeding, the mice were starved for 12 h. The blood sample from the eye was collected using the retro-orbital bleeding approach. The blood sample was naturally precipitated at 4 °C for 2 h, and then it was centrifuged at 3000 r/min and 4 °C for 10 min to separate the serum. The collected serum was stored at − 80 °C. The serum samples of 7 mice were randomly selected from each group and were used for the determination of the biochemical indicators MDA, SOD, GSH-Px, leptin and insulin using the corresponding assay kits.

Determination of monoamine neurotransmitters in mice brain

The mice were sacrificed by cervical dislocation. The whole brain of the mice was taken out, and it was frozen quickly using liquid nitrogen and was stored at − 80 °C. The brain samples of 7 mice from each group were used for the determination of the monoamine neurotransmitters using the corresponding assay kits. The brain sample was taken out and thawed, then it was dissolved in 0.9% saline at the ratio of 1:9 (w/v). And it was homogenized and centrifuged at 4 000 r/min for 5 min, and the supernatant was used for the determination of the contents of the four neurotransmitters using the assay kits.

A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used for the determination of the neurotransmitters using the kits. The samples, standards, and HRP markers were sequentially added to the coated micropores pre-coated with DA, 5-HT, NE and EPI antibodies. Then it was incubated and thoroughly washed. The substrate TMB was used for the color reaction. TMB was converted to blue under the catalysis of peroxidase and was then converted to the final yellow color by the action of an acid. The color depth was positively correlated with DA, 5-HT, NE and EPI content in the sample, respectively. The absorbance (OD value) was measured at 450 nm in the microplate reader of a Thermo Scientific Multiskan GO spectrophotometer (Thermo Fisher Scientific, Finland) to calculate the content using the standard curve. The standard curves of DA, 5-HT, NE and EPI were drawn using a series of standard concentrations as the horizontal coordinate, and the corresponding OD value as the vertical coordinate.

Statistical analysis

The mean values and standard deviations (SD) of the experimental data were calculated using Microsoft Office Excel 2013 (Microsoft Inc., Seattle, WA, USA). Significant differences between the different groups were analyzed by one-way ANOVA in SPSS Statistics 17.0 for Windows (SPSS, Inc., Chicago, IL).

Results and discussion

Effect of short-term intake of the four sweeteners on the body weight and feed intake of mice

The development of the body weight of mice after 32 days’ intake of the four sweeteners is shown in Table 1. The initial body weight of each group of mice was similar with each other, and there was no significant difference (p > 0.05). The body weight of the mice in each group increased gradually during the whole feeding process, and there was no significant difference (p > 0.05) between different groups. This indicates that the free drinking of 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution for 32 days will not affect the normal development of the body weight of the mouse. Tordoff et al. (2016) also found that there was no difference between the weight of the mice fed a diet including sucralose and the weight of the mice fed a common diet. Sweeteners may guide the choice of food, but short-term intake of these sweeteners may not result in significant changes in body weight. It is also reported that rebaudioside-A did not promote obesity in mice with a low fat or high fat diet (Reynolds et al. 2017). However, it has been suggested that the consumption of beverages with artificially sweeteners might promote obesity (Fowler et al. 2008), and saccharin might cause insulin resistance (Suez et al. 2014).

Table 1.

Effect of short-term intake of the four sweeteners on body weight of mice

Day Groups (g)
Control Sucralose Saccharin Maltose Stevioside
1 15.47 ± 1.23a 15.77 ± 1.07a 16.01 ± 0.81a 15.50 ± 1.05a 15.86 ± 1.08a
4 23.50 ± 1.62a 24.48 ± 1.68a 23.75 ± 1.06a 23.72 ± 1.41a 23.89 ± 1.66a
8 30.09 ± 1.91a 32.27 ± 2.24a 30.96 ± 1.43a 31.35 ± 2.01a 30.99 ± 1.46a
12 34.81 ± 2.06a 36.99 ± 2.72a 35.52 ± 2.05a 36.02 ± 2.79a 35.53 ± 1.80a
16 37.91 ± 2.47a 39.97 ± 3.29a 38.89 ± 2.19a 38.96 ± 2.94a 38.70 ± 2.12a
20 39.71 ± 2.57a 41.58 ± 3.58a 41.04 ± 2.61a 40.82 ± 3.06a 40.79 ± 1.99a
24 41.33 ± 2.93a 43.09 ± 4.46a 42.45 ± 2.37a 42.42 ± 3.08a 42.26 ± 2.09a
28 42.43 ± 3.02a 43.43 ± 4.47a 43.03 ± 2.40a 43.57 ± 3.29a 43.09 ± 1.96a
32 43.31 ± 2.94a 44.73 ± 4.44a 43.9 ± 2.49a 44.24 ± 3.76a 44.71 ± 2.35a
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Data were expressed as mean ± SEM (n = 10)

Different lower-case letters in the same row indicate significant difference (p < 0.05)

The change trend of feed intake of mice in each group is shown in Fig. 1. The feed intake of the mice in the 5 groups increased gradually in the first 10 days, and then it remained stable. There is no significant difference (p > 0.05) on the feed intake between the experimental groups and the control group during the whole feeding process. This indicates that the free drinking of 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution for 32 days will not affect the feed intake of the mice. Our previous study showed that the intake of sucrose could result in the decrease of the feed intake, and the reason might be that sucrose is a natural and energetic sweetener which can provide energy to the body, and this will result in the reduction of the energy from food and the decrease of feed intake (Yin et al. 2020). Maltose and stevioside are also natural sweeteners like sucrose. Although they have good characteristics of sweetness, their caloric value is not as high as sucrose. And this might be the reason that they do not affect the feed intake of mice.

Fig. 1.

Fig. 1

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Effect of short-term intake of the four sweeteners on feed intake of mice

Effect of short-term intake of the four sweeteners on the solution consumption on mice

The effect of short-term intake of the four sweeteners on the solution consumption of mice was shown in Fig. 2. In the first 8 days, the volumes of solution consumption in each group increased gradually and they were relatively close to each other. The solution consumption in the maltose group was higher than that in the control group during the whole feeding process with a significant difference after the 10th day (p < 0.05) except for day 12 and day 14, and there was a very significant difference after the 18th day (p < 0.01). The solution consumption in the sucralose group, saccharin group, stevioside group and control group increased gradually in the first 14 days, and then it became stable and there was no significant difference (p > 0.05) between each group.

Fig. 2.

Fig. 2

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Effect of short-term intake of the four sweeteners on the consumption of solution consumption on mice. Data were expressed as mean ± SEM (n = 7). *indicates significant difference (p < 0.05) between the sweetener group and control group, **indicates very significant difference (p < 0.01) between the sweetener group and control group

This result showed that the free drinking of 10 mM sucralose solution, 3 mM saccharin solution and 3 g/L stevioside solution for 32 days will not affect the consumption of these solutions on mice. While the 100 mM maltose solution could result in the sharp increase on the consumption of this solution. This indicates that although the tested four samples had similar sweetness, mice had the most preference for the carbohydrates like maltose, which also shows that the pure sweetness of carbohydrates is difficult to be replaced by other non-nutritive sweeteners. And this might due to different taste perception mechanisms involved in different sweeteners. It is quite different from sugars that artificial sweeteners have more than one taste descriptor, suggesting several different pathways are involved in their taste transduction, while sugars only have a single taste descriptor (Riera et al. 2008). It is supposed that rats have separate taste receptors for sugars and for starch-derived polysaccharides, and some researchers have found that maltose is the most preferred sugar on rats at low concentrations due to its stimulation of “polysaccharide” taste receptors (Sclafani and Mann 1987).

Effect of short-term intake of the four sweeteners on serum antioxidant indexes of mice

The effect of short-term intake of the four sweeteners on the content of MDA, SOD and GSH-Px in mice serum is shown in Fig. 3. The content of MDA in the serum of maltose and saccharin group increased significantly (p < 0.05) when compared with the control group (Fig. 3a), and they increased by 32.66% and 43.20%, respectively. The content of MDA in the saccharin group was the highest. The content of SOD in the serum of maltose and saccharin group decreased significantly (p < 0.05) when compared with the control group (Fig. 3b), and they decreased by 31.08% and 50.14%, respectively. The content of GSH-Px in the serum of maltose and saccharin group also decreased significantly (p < 0.05) when compared with the control group (Fig. 3c). And the content of SOD and GSH-Px in the saccharin group was the lowest. While there was no significant difference (p > 0.05) on the levels of MDA, SOD and GSH-Px in the sucralose group and stevioside group when compared with the control group. This result shows that maltose and saccharin will affect the levels of MDA, SOD and GSH-Px in serum of mice to varying degrees.

Fig. 3.

Fig. 3

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Effect of short-term intake of the four sweeteners on the content of MDA (a), SOD (b) and GSH-Px (c) in mice serum. Data were expressed as mean ± SEM (n = 7). Different lower-case letters indicate significant difference (p < 0.05) between different groups

Oxidative stress is an imbalance between oxidants and antioxidants that the oxidants could potentially cause damage to cells or cellular components (Sies 1997). The repair of oxidative stress is one of the antidiabetic effects and it is a state of metabolism equilibrium in which too many oxidizing free radicals in the muscle body coexist with a deficiency of antioxidants (Myint et al. 2020). MDA is a degradation product of polyunsaturated fatty acid peroxides, and it is used as an indicator of the level of oxidative stress. It is observed that stevioside could repair the oxidative stress in the STZ-induced diabetic mice (Myint et al. 2020), and the DPPH radical scavenging activity of 5 mg/mL stevioside is 1.03% (Sui 2015). Additionally, the reduction of the oxidative stress status using steviol glycosides in a fish model (Cyprinus carpio) was also observed (Sánchez-Aceves et al. 2017). However, the intake of stevioside solution did not affect the content of MDA, SOD and GSH-Px in mice in the present study, and the reason should be that the lower concentration of stevioside solution at 3 g/L was used in this study.

The result of the present study indicates that saccharin had the strongest effect on the content of MDA, SOD and GSH-Px in mice serum among those four sweeteners. Amin and AlMuzafar (2015) found that high dose of saccharin at 500 mg/kg bw could also result in the significant increase (p < 0.05) of MDA and decrease (p < 0.05) of SOD and GSH in rats, while the low dose of saccharin at 10 mg/kg bw had no significant effect on these indicators, and they pointed out that the reason for this oxidative stress might be the inflammation initiated to the liver cells. And this speculation is supported by other study that the moderate infiltration of mononuclear inflammatory cells in portal tract of rat liver was observed after they were received saccharin for 6 weeks (Hassanin 1998). It is reported that saccharin could produce ROS and lipid peroxidation to the lipid of hepatic cell membranes and these ROS could result in the depletion of GSH, SOD and catalase which were used to reduce the toxic action of liberated oxygen radical (Amin and AlMuzafar 2015). The result obtained in the present study also showed that the 100 mM maltose solution and 3 mM saccharin solution which were the most preferred concentrations of mice could result in the oxidative stress on mice after 32 days’ short-term intake.

Effect of short-term intake of the four sweeteners on the content of leptin and insulin on mice

The effect of short-term intake of the four sweeteners on the content of leptin and insulin on mice is shown in Fig. 4. As shown in Fig. 4a, the leptin levels in the sucralose group, maltose group, saccharin group, and stevioside group increased significantly (p < 0.05) when compared with the control group. There was no significant difference on the levels of leptin between the maltose group and the saccharin group (p > 0.05). The highest and lowest increase of leptin in the stevioside group and sucralose group was observed respectively. Leptin is an adipose tissue hormone that acts as an incoming signal in a negative feedback loop to maintain steady-state control of the quality of adipose tissue (Friedman 2004). Leptin can be used as a body balance signal to control food intake. Studies have shown that leptin can reduce food intake by reducing the reward value of sucrose (Domingos et al. 2014). The mechanism of leptin on dopamine signaling is unclear, but leptin receptors can be expressed in dopamine neurons in the ventral tegmental area (VTA) of the brain (Hommel et al. 2006). In addition, leptin can increase the level of tyrosine hydroxylase and increase the sensitivity to amphetamine, and these phenomena indicate that leptin has an excitatory effect on the reward pathway (Domingos et al. 2011).

Fig. 4.

Fig. 4

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Effect of short-term intake of the four sweeteners on the content of leptin (a) and insulin (b) in mice serum. Data were expressed as mean ± SEM (n = 7). Different lower-case letters indicate significant difference (p < 0.05) between different groups

As shown in Fig. 4b, the insulin levels in the sucralose group, maltose group, saccharin group, and stevioside group increased significantly (p < 0.05) when compared with the control group. And it was the highest in the stevioside group. This result indicates that the short-term intake of sucralose, maltose, saccharin, and stevioside solutions for 32 days would result in the increase of the insulin levels in the serum of mice, resulting in the occurrence of insulin resistance. It is reported that the intake of sucrose could induce insulin resistance whether it was added to the feed or direct gavage (Matsumoto et al. 2009). Artificial sweeteners are widely used in the food industry. Although their metabolism does not depend on insulin, the mechanism of influence on insulin resistance needs further investigation. Previous study showed that the stevia extract (Rebaudioside-A) could increase the secretion of insulin by the inhibition of ATP-dependent potassium channels and suppress the secretion of glucagon by alpha cells of the pancreas and not by the action of incretin hormones (Pepino 2015). The antidiabetic effects on diabetic mice were also observed by lowering blood sugar, reducing insulin resistance and HbA1c level, improving glucose tolerance and reducing liver glycogen level of the diabetic mice (Myint et al. 2020).

Effect of short-term intake of the four sweeteners on the release of monoamine neurotransmitters in mice brain

The effect of short-term intake of the four sweeteners on the release of monoamine neurotransmitters in mice brain is shown in Fig. 5. Sugars that can be hydrolyzed into small molecule glucose (such as maltose) will induce the release of DA in the striatum, which will produce a rewarding effect after being broken down. Therefore, it is usually more widely used than artificial sweeteners, and the neural circuit that mediates the reward effect of glucose is still unknown. Although artificial sweeteners do not have the rewarding effect of sugar intake, they have the same nutritional value and can increase the attractiveness of food (Domingos et al. 2013). Studies have shown that mice can form dependent behaviors based on post-ingestion effects, and the integrity of dopaminergic neurons and vagus nerves in the ventral tegmental area (VTA) of the brain is essential for the formation of dependent behavior (Fernandes et al. 2017). As shown in Fig. 5a, the DA content in the whole brain of the mice in the maltose group increased significantly (p < 0.05) when compared with mice in the control group. This result is the same with the result of solution consumption in the maltose group in Fig. 2 that the significant increase in drinking volume of maltose solution was observed. This indicates that the intake of maltose solution could result in the synthesis and release of DA in the mouse brain, which would stimulate its continuous intake of maltose and stimulate the reward effect of the post-ingestion effects.

Fig. 5.

Fig. 5

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Effect of short-term intake of the four sweeteners on the release of monoamine neurotransmitters in mice brain (a dopamine, DA; b 5-hydroxytryptamine, 5-HT; c norepinephrine, NE; d epinephrine, EPI). Data were expressed as mean ± SEM (n = 7). Different lower-case letters indicate significant difference (p < 0.05) between different groups

As shown in Fig. 5b, the 5-HT levels in the whole brain of the sucralose group (p > 0.05), maltose group (p < 0.05), saccharin group (p < 0.05), and stevioside group (p < 0.05) increased when compared with the control group. And it was the highest in the stevioside group. 5-HT is also a monoamine neurotransmitter like DA, and its release can stimulate the production of pleasant emotions and increase excitement. This result shows that in addition to the natural sweeteners maltose and stevioside, the intake of artificial sweeteners sucralose and saccharin can also stimulate the rewarding effect of mice and induce the secretion of the monoamine neurotransmitter 5-HT.

As shown in Fig. 5c, there was no significant difference (p > 0.05) on the content of NE in the sucralose group, maltose group, saccharin group and stevioside group when compared with the control group. As shown in Fig. 5d, there was no significant difference (p > 0.05) on the content of EPI between the sucralose group and the control group. While it was increased significantly (p < 0.05) in the maltose group, saccharin group and stevioside group when compared with the control group. And it was the highest in the stevioside group.

The above results indicate that the release of dopamine is the main factor affecting the pleasant mood during the performance of the liking behavior, which can be observed from the massive intake of the maltose solution. Sucralose is a non-caloric artificial sweetener. Although the mice showed a strong preference for sucralose in the double-bottle preference experiment (Yin et al. 2020), this artificial sweetener did not affect the secretion of monoamine neurotransmitters in mice. Saccharin and stevioside could increase the levels of 5-HT and EPI in the brain of mice, but it had no effect on the content of DA. And this indicates that only sugars that can be broken down into small molecules of glucose may have a positive effect on dopamine levels.

There were no significant changes (p > 0.05) on these four tested monoamine neurotransmitters in the sucralose group. This indicates that sucralose should be an ideal sugar substitute that could be used in food and drinks for controlling the body weight and blood glucose. It is also reported that the use of sucralose did not affect the concentrations of glycosylated hemoglobin, but it might stimulate the flavor receptors and GLUT2 receptors which could stimulate the intestinal absorption of glucose (Mace et al. 2007).

In this study, the short-term intake of the 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution did not affect the body weight and feed intake of the mice. This indicates that the increase of DA, 5-HT and EPI during the 32 days’ short-term feeding will not affect the changes in body weight. While the long-term (8 month) intake of 10% sucrose solution could result in the increase in solution consumption and body weight of mice, and this was associated with the decrease of DA in the striatum (Ahmed et al. 2014). Among the 4 tested sweeteners, maltose solution was the preferred solution which could increase the DA secretion. The consumption of palatable food which could increase DA release has been reported in previous research (Hajnal et al. 2008), and the increased striatal DA may inhibit its synthesis ultimately via the feedback inhibition of tyrosine hydroxylase activity (Wallace 2007), which is similar to the chronic exposure to alcohol (Kashem et al. 2012). Dopamine is a neurotransmitter which plays a critical role in the regulation of energy intake and body weight (Goldfield et al. 2013). It is also an important role in the development of obesity, and compensatory eating due to hypofunctionality of the dopaminergic system can not only due to the genetically determined factors, but may also be induced by preceding overstimulation with natural stimulation or pharmacological enhancement (Reinholz et al. 2008). It is found that chronic systemic administration of 5-HT can produce considerable weight loss in rats (Edwards 1995). NE and EPI are the two catecholamines which can affect practically the function of all body tissues, organs, and systems. It is reported that the infusion of NE could inhibit body weight gain while EPI-infused rats gained more weight than controls (Racotta et al. 1986). Interesting, it is observed in this study that maltose, saccharin and stevioside could promote the release of 5-HT, but also increase the content of EPI. Generally, although the short-term intake of maltose, saccharin and stevioside can influence the release of the neurotransmitters, it does not result in significant change on the body weight.

Conclusion

The effect of preferred concentrations of natural sweeteners (maltose, stevioside) and artificial sweeteners (sucralose, saccharin) on feed intake, solution consumption and neurotransmitters release on mice after short-term intake was investigated in the present study. These obtained results showed that the short-term intake of the preferred concentrations of maltose, stevioside, sucralose and saccharin will not affect the body weight and feed intake of the mice. Mice prefer maltose solution to other three sweeteners solutions. The 100 mM maltose solution and 3 mM saccharin solution could result in the oxidative stress on mice after 32 days’ short-term intake. Compared with other sweeteners, only sugars that could be broken down into small molecules of glucose might have a positive effect on dopamine levels.

Acknowledgements

This study was supported by the National Key Research and Development Plan of China (2017YFD0400101) and the Fundamental Research Funds for the Central Universities (Program No. 2662020SPPY002).

Compliance with ethical standards

Conflict of interest

The authors have declared that there is no conflict of interest.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Jing-Nan Ren and Kai-Jing Yin have contributed equally to this work.

References

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