Browsing by Author "Henry, Curtis J."

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    Consumption of Diet Soda Sweetened with Sucralose and Acesulfame‐Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity
    (Wiley, 2020-06) Sylvetsky, Allison C.; Sen, Sabyasachi; Merkel, Patrick; Dore, Fiona; Stern, David B.; Henry, Curtis J.; Cai, Hongyi; Walter, Peter J.; Crandall, Keith A.; Rother, Kristina I.; Hubal, Monica J.; Kinesiology, School of Health and Human Sciences
    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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    Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
    (Springer Nature, 2022-03-03) Lee, Miyoung; Hamilton, Jamie A.G.; Talekar, Ganesh R.; Ross, Anthony J.; Michael, Langston; Rupji, Manali; Dwivedi, Bhakti; Raikar, Sunil S.; Boss, Jeremy; Scharer, Christopher D.; Graham, Douglas K.; DeRyckere, Deborah; Porter, Christopher C.; Henry, Curtis J.; Pediatrics, School of Medicine
    The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance.