Bridi, L. | bioRxiv Science

bioRxiv2021

Lasting effects of low-calorie sweeteners on glucose regulation, sugar intake, and memory

Low-calorie sweetener (LCS) consumption in children has increased due to widespread LCS presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the impact of early-life LCS consumption are lacking. Therefore, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, gut microbiome, neural, and behavioral outcomes. Results reveal that habitual early-life LCS consumption disrupts post-oral glucose tolerance and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, LCS consumption reduces lingual sweet taste receptor expression and alters sugar-motivated appetitive and consummatory responses. RNA sequencing analyses reveal that LCS also impacts collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results suggest that regular early-life LCS consumption yields long-lasting impairments in metabolism, sugar-motivated behavior, and hippocampal-dependent memory.

neuroscience↗

bioRxiv2021

Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention

ObjectiveConsumption of a Western diet during adolescence results in hippocampus (HPC)-dependent memory impairments and gut microbiome dysbiosis. Whether these adverse outcomes are reversible in adulthood following intervention with a healthy diet is unknown. Here we assessed the short- and long-term effects of adolescent consumption of a Western diet enriched with either sugar alone, or sugar and fat on metabolic outcomes, HPC-dependent memory, and gut microbiota. MethodsAdolescent female rats (PN 26) were fed a standard chow diet (CTL), a chow diet with access to 11% sugar solution (SUG), or a junk food cafeteria-style diet (CAF) containing a variety of fat- and/or sugar-enriched foods. During adulthood (PN 65+), metabolic outcomes, HPC-dependent memory, and gut microbial populations were evaluated both before and after a 5-week dietary intervention period where all groups were fed a diet of water standard chow. ResultsPrior to the dietary intervention both the CAF and SUG groups demonstrated impaired HPC-dependent memory, increased adiposity, and altered gut microbial populations relative to controls. However, impaired peripheral glucose regulation was only observed in the SUG group. The dietary intervention reversed the metabolic dysfunction in both the CAF and SUG groups, whereas HPC-dependent memory impairments were reversed in the SUG, but not the CAF group. The composition of the gut microbiota remained distinct from controls in both groups after dietary intervention. ConclusionsWhile the metabolic impairments associated with adolescent cafeteria diet consumption are reversible in adulthood with dietary intervention, the HPC-dependent memory impairments and the gut microbiome dysbiosis persist.

developmental biology↗