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. 2017 May 5;12(5):e0177138.
doi: 10.1371/journal.pone.0177138. eCollection 2017.

Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice

Thomas H Reynolds 4th  1 , Rachelle A Soriano  1 , Obadi A Obadi  1 , Stanley Murkland  1 , Bernard Possidente  1
Affiliations

Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice

Thomas H Reynolds 4th et al. PLoS One. .

Abstract

Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda), can reduce caloric intake and possibly facilitate weight loss. The purpose of the present study was to examine the effects of the artificial sweetener, rebaudioside A (Reb-A), on circadian rhythms, in vivo insulin action, and the susceptibility to diet-induced obesity. Six month old male C57BL/6 mice were assigned to a control or Reb-A (0.1% Reb-A supplemented drinking water) group for six months. Circadian wheel running rhythms, body weight, caloric intake, insulin action, and susceptibility to diet-induced obesity were assessed. Time of peak physical activity under a 12:12 light-dark (LD) cycle, mean activity levels, and circadian period in constant dark were not significantly different in mice that consumed Reb-A supplemented water compared to normal drinking water, indicating that circadian rhythms and biological clock function were unaltered. Although wheel running significantly reduced body weight in both Reb-A and control mice (P = 0.0001), consuming Reb-A supplemented water did not alter the changes in body weight following wheel running (P = 0.916). In vivo insulin action, as assessed by glucose, insulin, and pyruvate tolerance tests, was not different between mice that consumed Reb-A treated water compared to normal drinking water. Finally, Reb-A does not appear to change the susceptibility to diet-induced obesity as both groups of mice gained similar amounts of body weight when placed on a high fat diet. Our results indicate that consuming Reb-A supplemented water does not promote circadian disruption, insulin resistance, or obesity.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Rebaudioside A treatment does not alter circadian wheel running activity.
Effects of Reb-A treatment on circadian running wheel activity rhythms were assayed while mice consumed a standard rodent diet with free-access to running wheels. Panel A shows representative actograms for wheel running activity for 14 days in a 12:12 LD cycle immediately followed by 10 days in constant darkness. The x-axis represents 48 hours of activity, and the Y-axis represents 24 consecutive days from top to bottom. Activity cycles are double-plotted so that each row shows two consecutive days of activity, with the second day in each row repeated as the first day in the next. Panel B shows mean activity levels during the 14 days of LD, and panel C shows the time of peak activity in LD. Panel D shows mean activity levels in DD and panel E shows the circadian period in DD. N = 10 mice per group.
Fig 2
Fig 2. Rebaudioside A treatment does not alter weight loss following circadian wheel running activity.
Mice were fed a standard rodent diet for and given free access to a running wheel. Body weight was measured before and after 32 days of wheel running. *, Denotes statistically significant changes in body weight following the wheel running intervention within respective groups of mice. N = 10 mice per group.
Fig 3
Fig 3. Long-term Reb-A treatment does not alter insulin action.
Mice were injected with 1.0 g/Kg glucose (A and B), 0.5 U//Kg insulin (C and D), or 1.0 g/Kg pyruvate (E and F) and blood glucose values were assessed at baseline at 0, 15, 30, 45, 60, and 90 min following the injection. The area under the curve was calculated for glucose levels following the respective injections (Panels B, D, and F). N = 8 mice per group.
Fig 4
Fig 4. Reb-A does not alter the body weight response to a HFD.
Body weight was assessed before and following 18 weeks of a HFD in mice treated with Reb-A or vehicle. *, Denotes statistically significant difference from respective vehicle group by LSD post-hoc analysis (P = 0.0001) conduct after a significant ANOVA main effect for diet (P = 0.0001). N = 8 mice per group.
Fig 5
Fig 5. Reb-A does not alter the caloric intake response to a HFD.
Caloric intake was assessed before and following 18 weeks of a HFD in mice treated with Reb-A or vehicle. One way ANOVA revealed no significant main effects for Reb-A treatment (P = 0.325) or diet (P = 0.095). N = 8 mice per group.
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Grants and funding

This work was supported by a Skidmore College Faculty Development grant awarded to BP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.