The purpose of this study is to determine whether eight weeks of low-calorie sweetener (LCS) exposure exerts cardiovascular and/or metabolic effects among LCS-naïve overweight and obese adolescents and young adults. We will examine changes in gene expression in subcutaneous fat and will correlate these molecular changes with plasma biochemistry.

The proposed study will investigate LCS-induced changes in metabolically "at-risk" young adults, under conditions that reflect typical beverage consumption. We will first identify molecular pathways potentially affected by LCS (adipose transcriptomics via global RNAseq) and then identify links between LCS-induced gene expression changes and circulating levels of key metabolic biomarkers and clinical outcomes. We will perform subcutaneous adipose biopsies before and after consumption of 12 ounces of diet soda three times daily for eight weeks. Within-subjects changes in adipose gene expression will be evaluated using RNAseq. We will then correlate transcriptomic changes with circulating levels of key inflammatory and metabolic biomarkers, to provide mechanistic insight into which pathways drive clinically-relevant LCS-induced metabolic impairments. We will measure glucose, insulin, inflammatory markers and adipose-derived hormones before and after eight weeks of LCS exposure.

Inclusion Criteria:

1. Female
2. 18-25 years of age
3. Overweight and mild to moderate obesity (25 ≤ body mass index (BMI) <35 kg/m2)
4. Consumption of <1 food/beverage with sucralose and/or acesulfame-potassium per month
5. Able and willing to comply with all study procedures for the duration of the study

Exclusion Criteria:

1. Overt diabetes
2. Renal/gastrointestinal conditions
3. Pregnant/lactating
4. Recent significant weight change
5. Acute illness (w/fever)
6. Antibiotics in past 3 months
7. Use of illegal drugs/condition limiting ability to give consent.