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 aimed to identify molecular pathways in adipose impacted by LCS consumption.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 fasting blood sample were collected at baseline and post-intervention. Global gene expression changes 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 including interleukins and tumor-necrosis-family members. Fifty-eight of 140 canonical pathways represented in pathway analyses regulate inflammation, and several key upstream regulators of inflammation (e.g. TNF-alpha) were also represented.Consumption of diet soda with sucralose and Ace-K altered inflammatory transcriptomic pathways (e.g. NF-κB signaling) in subcutaneous adipose tissue but did not significantly alter circulating biomarkers. These findings highlight the need to examine molecular and metabolic effects of LCS exposure in a larger randomized control trial for a longer duration. This article is protected by copyright. All rights reserved.
