Scope 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.

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Objective: To compare the sugar content of items at four multinational fast-food chains, across three countries. Design: Total sugar (g)/per serving was extracted from online nutrition information, and sugar/100 g serving was calculated. Foods were categorised as: breakfast sandwiches, burgers, sandwiches, desserts and condiments. Beverages were categorised as fountain, frozen or pre-packaged. Sugar (g) was compared across countries using linear mixed-effects models. Pairwise comparisons were performed with Tukey–Kramer adjustments. Setting: USA, Germany and Australia. Participants: Burger King™ (Hungry Jack’s™), Kentucky Fried Chicken™, McDonald’s™ and Subway™. Results: Differences in total sugar/100 g or ml were observed across countries for burgers (n 104), desserts (n 110), sandwiches (n 178), pre-packaged beverages (n 36) and frozen beverages (n 72). Comparing identical items across countries (e.g. BigMacTM from McDonalds in USA, Germany and Australia), burgers (n 10 available in all three countries) had lower sugar content in Australia (3·4 g/100 g) compared with the USA (4·7 g/100 g, P = 0·02) or Germany (4·6 g/100 g, P = 0·04), yet no differences were observed in other food categories. Comparing the same beverages across countries (e.g. chocolate shake from Burger King), frozen beverages (n 4 available in all three countries) had lower sugar content in Australia (14·2 g/100 ml), compared with the USA (20·3 g/100 ml, P = 0·0005) or Germany (17·8 g/100 ml, P = 0·0148), yet no differences were observed in other beverage categories. Conclusions: Heterogeneity in fast-food sugar content across countries suggests that reductions are possible and should be implemented to reduce health risks associated with excess added sugar intake.