Dataset Information

Early life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

ABSTRACT: Low-calorie sweetener (LCS) consumption in children has increased dramatically due to widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal post-oral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and alterations in sugar-motivated appetitive and consummatory responses. While early life LCS consumption did not produce robust changes in the gut microbiome, brain region-specific RNA sequencing analyses reveal LCS-induced changes in collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE212589 | GEO | 2022/09/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders, including Alzheimer’s Disease (AD). In many cases, chemosensory deficits are harbingers of neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into the fundamental dysfunction associated with aging and neurodegeneration. The fruit fly, Drosophila melanogaster, is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging and neurodegeneration on chemosensation remain largely unexplored in this model, particularly with respect to taste. To determine whether the effects of aging on taste are conserved in flies, we compared the response of flies to different appetitive tastants. Aging impaired response to sugars, but not medium-chain fatty acids that are sensed by a shared population of neurons, revealing modality-specific deficits in taste. Selective expression of the human amyloid beta (Ab) 1-42 peptide bearing the Arctic mutation (E693E) associated with early onset AD in the neurons that sense sugars and fatty acids phenocopies the effects of aging, suggesting that the age-related decline in response is localized to gustatory neurons. Functional imaging of gustatory axon terminals revealed reduced response to sugar, but not fatty acids. Axonal innervation of the fly taste center was largely intact in aged flies, suggesting that reduced sucrose response does not derive from neurodegeneration. Conversely, expression of the amyloid peptide in sweet-sensing taste neurons resulted in reduced innervation of the primary fly taste center. A comparison of transcript expression within the sugar-sensing taste neurons revealed age-related changes in 66 genes, including a reduction in odorant-binding protein class genes that are also expressed in taste sensilla. Together, these findings suggest that deficits in taste detection may result from signaling pathway-specific changes, while different mechanisms underly taste deficits in aged and AD model flies. Overall, this work provides a model to examine cellular deficits in neural function associated with aging and AD.

Dataset Information

Early life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets