Sylvetsky, Allison C.Sen, SabyasachiMerkel, PatrickDore, FionaStern, David B.Henry, Curtis J.Cai, HongyiWalter, Peter J.Crandall, Keith A.Rother, Kristina I.Hubal, Monica J.2023-03-032023-03-032020-06Sylvetsky, A. C., Sen, S., Merkel, P., Dore, F., Stern, D. B., Henry, C. J., Cai, H., Walter, P. J., Crandall, K. A., Rother, K. I., & Hubal, M. J. (2020). Consumption of Diet Soda Sweetened with Sucralose and Acesulfame‐Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity. Molecular Nutrition & Food Research, 64(11), 1901166. https://doi.org/10.1002/mnfr.2019011661613-4125, 1613-4133https://hdl.handle.net/1805/31607SCOPE: Low-calorie sweetener (LCS) consumption is associated with metabolic disease in observational studies. However, physiologic mechanisms underlying LCS-induced metabolic impairments in humans are unclear. This study is aimed at identifying molecular pathways in adipose impacted by LCSs. METHODS AND RESULTS: Seven females with overweight or obesity, who did not report LCS use, consumed 12 ounces of diet soda containing sucralose and acesulfame-potassium (Ace-K) three times daily for 8 weeks. A subcutaneous adipose biopsy from the left abdomen and a fasting blood sample were collected at baseline and post-intervention. Global gene expression were assessed using RNA-sequencing followed by functional pathway analysis. No differences in circulating metabolic or inflammatory biomarkers were observed. However, ANOVA detected 828 differentially expressed annotated genes after diet soda consumption (p < 0.05), including transcripts for inflammatory cytokines. Fifty-eight of 140 canonical pathways represented in pathway analyses regulated inflammation, and several key upstream regulators of inflammation (e.g., TNF-alpha) were also represented. CONCLUSION: Consumption of diet soda with sucralose and Ace-K alters inflammatory transcriptomic pathways (e.g., NF-κB signaling) in subcutaneous adipose tissue but does not significantly alter circulating biomarkers. Findings highlight the need to examine molecular and metabolic effects of LCS exposure in a larger randomized control trial for a longer duration.en-USPublisher PolicyAdipose TissueGene Expression RegulationmetabolismArtificially Sweetened BeveragesArticle