Abstract P117: Weight Loss is Associated With Increases in Mitochondrial DNA Copy Number

Abstract

Background: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function that is independently associated with increased cardiovascular disease risk. Individuals with obesity and cardiometabolic risk factors have lower mtDNA-CN levels. However, the modifiability of mtDNA-CN following a weight loss intervention has remained largely unexplored. Hypothesis: Bariatric surgery-induced weight loss is associated with longitudinal increases in circulating mtDNA-CN levels. Methods: In the BARI-Heart prospective cohort of bariatric surgery patients, we quantified mtDNA-CN from whole blood samples collected at three visits: 3 to 6 months prior to surgery, 2-4 weeks prior to surgery, and 6 months post-surgery. We used linear mixed models with random effects to assess changes in mtDNA-CN after bariatric surgery, with the pre-surgery visits while awaiting bariatric surgery serving as the control period. We used multivariable linear regression to evaluate the dose-response association between weight loss and change in mtDNA-CN. Results: We included 71 participants (mean age 45 years, 74% female, 88% White). While mtDNA-CN levels did not change significantly during the pre-surgery period (V1 to V2), mtDNA-CN significantly increased after bariatric surgery (V2 to V3) (Figure). In linear mixed models adjusting for age, sex, and smoking, mtDNA-CN was higher after bariatric surgery than immediately prior to bariatric surgery (Table: ß=0.141, p < 0.001). This increase in mtDNA-CN remained significant following further adjustment for changes in cardiometabolic risk factors (ß=0.116, p < 0.01). In linear regression, each 10% greater weight loss was associated with a 1.6% increase in mtDNA-CN. Conclusions: Weight loss via bariatric surgery is associated with significant increases in mtDNA-CN, independent of cardiometabolic risk factors. Improvements in mitochondrial function may mediate some of the cardiovascular benefits of significant weight loss.