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However, physiologic mechanisms underlying LCS\u2010induced metabolic impairments in humans are unclear. This study is aimed at identifying molecular pathways in adipose impacted by LCSs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Seven females with overweight or obesity, who did not report LCS use, consumed 12 ounces of diet soda containing sucralose and acesulfame\u2010potassium (Ace\u2010K) 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\u2010intervention. Global gene expression were assessed using RNA\u2010sequencing 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 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), including transcripts for inflammatory cytokines. Fifty\u2010eight of 140 canonical pathways represented in pathway analyses regulated inflammation, and several key upstream regulators of inflammation (e.g., TNF\u2010alpha) were also represented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Consumption of diet soda with sucralose and Ace\u2010K alters inflammatory transcriptomic pathways (e.g., NF\u2010\u03baB 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201901166","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T10:59:53Z","timestamp":1586775593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Consumption of Diet Soda Sweetened with Sucralose and Acesulfame\u2010Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0424-2798","authenticated-orcid":false,"given":"Allison C.","family":"Sylvetsky","sequence":"first","affiliation":[{"name":"Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health The George Washington University  950 New Hampshire Avenue NW Washington DC 20052 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabyasachi","family":"Sen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology George Washington University School of Medicine  2120 L. 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