Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats

Abstract

The use of high-intensity sweeteners has been proposed as a method to combat increasing rates of overweight and obesity in the human population. However, previous work with male rats suggests that consumption of such sweeteners might contribute to, rather than ameliorate, weight gain. The goals of the present experiments were to assess whether intake of high-intensity sweeteners is associated with increased food intake and body weight gain in female rats; to evaluate whether this effect depends on composition of the maintenance diet (i.e., standard chow compared with diets high in energy, fat, and sugar [HE diets]); and to determine whether the phenotype of the rats with regard to propensity to gain weight on HE diets affects the consequences of consuming high-intensity sweeteners. The data demonstrated that female rats fed a low-fat, standard laboratory chow diet did not gain extra weight when fed yogurt dietary supplements sweetened with saccharin compared with those fed glucose-sweetened dietary supplements. However, female rats maintained on a "Westernized" diet high in fat and sugar (HE diet) showed significant increases in energy intake, weight gain, and adiposity when given saccharin-sweetened compared with glucose-sweetened yogurt supplements. These differences were most pronounced in female rats known to be prone to obesity prior to the introduction of the yogurt diets. Both selectively bred Crl:OP[CD] rats and outbred Sprague-Dawley rats fed an HE diet showing high levels of weight gain (diet-induced obese [DIO] rats) had increased weight gain in response to consuming saccharin-sweetened compared with glucose-sweetened supplements. However, in male rats fed an HE diet, saccharin-sweetened supplements produced extra weight gain regardless of obesity phenotype. These results suggest that the most negative consequences of consuming high-intensity sweeteners may occur in those most likely to use them for weight control, females consuming a "Westernized" diet and already prone to excess weight gain.

Figure 1

Body weight gain in female rats consuming low-fat standard laboratory chow diet was not affected by the type of sweetener provided in a daily yogurt dietary supplement.

Figure 2

Body weight gain in DIO female rats (panel A) was significantly greater when consuming Saccharin-sweetened yogurt along with a chow diet high in sugar and fat compared to those given Glucose-sweetened yogurt. In contrast, DR females (B) showed no differences in body weight gain based on the type of sweetener consumed. Filled circles = saccharin-sweetened yogurt; white squares = glucose-sweetened yogurt. Fat mass (C) was significantly higher in DIO animals given Saccharin-sweetened yogurt compared to DIO animals given Glucose-sweetened yogurt. Lean mass (D) was higher in females given Saccharin-sweetened yogurt compared to females given Glucose-sweetened yogurt across both phenotypes. * p < .05 compared to DIO Glucose # p < .05 between Glucose and Saccharin

Figure 3

A) In DIO animals fed a diet high in saturated fat and sugar across 4 weeks of yogurt exposure, caloric intake from yogurt was significantly higher in female rats consuming glucose-sweetened yogurt compared to DIO rats consuming saccharin-sweetened yogurt, while both caloric intake from the HE diet and total caloric intake (from HE diet plus yogurt) was significantly greater in animals consuming the saccharin-sweetened yogurt. B) In DR females, energy intake from yogurt was higher in females given the glucose-sweetened yogurt and intake from the HE diet was significantly higher in females given the saccharin-sweetened yogurt. However, total caloric intake in DR female rats did not differ between saccharin and glucose groups. * p < .05 compared to glucose group

Figure 4

Body weight gain in DIO female rats (panel A) was significantly greater when consuming Saccharin-sweetened yogurt along with a chow diet high in sugar and fat compared to those given Glucose-sweetened yogurt. In contrast, DR females (B) showed no differences in body weight gain based on the type of sweetener consumed. Fat mass (C) was significantly greater in female DIO rats compared to female DR rats, while lean mass (D) was significantly greater in females that consumed Saccharin-sweetened yogurt compared to females that consumed Glucose-sweetened yogurt. # p < .05 compared to DR * p < .05 compared to Glucose

Figure 5

Body weight gain in male rats was significantly greater when consuming Saccharin-sweetened yogurt along with a chow diet high in sugar and fat compared to those given Glucose-sweetened yogurt in both DIO (A) and DR (B) phenotypes. *p < .05 compared to glucose-sweetened group

Figure 6

Body weight gain in offspring of selectively bred OP rats (A) and OR rats (B) given saccharin-sweetened yogurt did not differ from same-phenotype females during the first week of yogurt exposure when a standard low-fat laboratory chow was provided along with the sweetened yogurt. However, body weight gain was significantly higher during the last 2 weeks of yogurt when OP rats were given Saccharin-sweetened yogurt and an HE diet compared to glucose-sweetened yogurt and the HE diet. These effects were more pronounced in OP females compared to OR females, where only a trend towards increased weight gain in the animals consuming the saccharin-sweetened diet was observed. C) Fat mass was significantly greater in female OP and OR rats that consumed Saccharin-sweetened yogurt compared to females that consumed Glucose-sweetened yogurt, while lean mass (D) did not differ significantly based on sweetener or phenotype. * p < .05 compared to Glucose-sweetened yogurt