CHROMATIN ACCESSIBILITY CHANGES IN ADIPOSE TISSUE CONTRIBUTING TO THE METABOLIC BENEFITS OF BARIATRIC SURGERY
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Many adverse health outcomes result from dysregulation of cellular processes such as cell-cell signaling, transcription, protein modifications, and cellular metabolism. This includes obesity, leading to detrimental health outcomes involving type 2 diabetes and cardiometabolic disease. Vertical sleeve gastrectomy (VSG), a surgical obesity treatment, results in long-term weight loss and remission of type 2 diabetes in most patients. Some effects of VSG are independent of body weight, and the mechanisms behind the metabolic benefits are not fully understood. I performed single-nucleus ATAC-seq on adipose tissues from a VSG mouse model to reveal the mechanisms regulating adipose tissue and its contribution to the VSG-induced metabolic improvements. We observed depot-specific cellular composition and chromatin accessibility patterns altered by VSG. In particular, VSG reduced the accessibility of Scd1, which encodes a fatty acid desaturase. Additionally, SCD1-produced monounsaturated fatty acids were less abundant, meaning SCD1 activity was reduced. Obesity and insulin resistance are positively correlated with SCD1 activity, suggesting that the VSG-induced reduction in accessibility and activity of SCD1 acts as a metabolic switch in adipocytes, potentially leading to whole-body insulin sensitivity. These findings provide insights into how alterations to adipose lipid metabolism could contribute to the beneficial effects of VSG.
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Cummings, Bethany P.
Roberson, Mark Stephen