Beyond the surface: mapping DDE's metabolic footprint on adolescent obesity

Authors: LI, ZHENJIANG - University Of Southern California; PAN, SHUDI - University Of Southern California; BAUMERT, BRITTNEY - University Of Southern California; CHEN, JIAWEN - University Of Southern California; GOODRICH, JESSE - University Of Southern California; WANG, HONGXU - University Of Southern California; ROCK, SARAH - University Of Southern California; RYDER, JUSTIN - Northwestern University; VALVI, DAMASKINI - The Icahn School Of Medicine At Mount Sinai; JENKINS, TODD - University Of Cincinnati College Of Medicine; SISLEY, STEPHANIE - Baylor College Of Medicine; LIN, XIANGPING - Stanford University School Of Medicine; BARTELL, SCOTT - University Of California Irvine; INGE, THOMAS - University Of Cincinnati College Of Medicine; XANTHAKOS, STAVRA - University Of Cincinnati College Of Medicine; MCNEIL, BROOKLYN - Columbia University - New York; ROBUCK, ANNA - University Of Rhode Island; MULLINS, CATHERINE - Emory University; ECKEL, SANDRAH - University Of Southern California; MCCONNELL, ROB - University Of Southern California; LA MERRILL, MICHELE - University Of California, Davis; WALKER, DOUGLAS - Emory University; CONTI, DAVID - University Of Southern California; CHATZI, LIDA - University Of Southern California

Submitted to: Environmental Health Perspectives
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/15/2025
Publication Date: N/A
Citation: N/A
DOI: https://doi.org/10.1289/ehp16341

Interpretive Summary: Bariatric surgery helps teens with severe obesity lose weight and improve their health. But when fat is burned during weight loss, it can release harmful chemicals stored in the body. One of these chemicals is called DDE, which may actually make it harder to lose weight. This study looked at 60 teens who had weight-loss surgery. Samples of their body fat and blood were tested for DDE and other substances before and after surgery. The goal was to see how DDE might affect weight loss. The results showed that DDE changed certain chemicals in the body, both in fat and in blood. One chemical, called methylbutyroylcarnitine, was linked to both DDE levels and body weight. This suggests that DDE might interfere with how well the surgery works by changing how the body handles energy and fat. These findings show that chemicals from the environment, like DDE, could make it harder to keep weight off after surgery. Doctors may need to think about these chemicals when helping patients with obesity.

Technical Abstract: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored. We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics. We conducted a longitudinal study involving 60 adolescents with severe obesity undergoing bariatric surgery. We quantified p,p'-DDE concentrations in visceral adipose tissue collected during surgery and analyzed metabolic profiles from both adipose tissues collected at surgery and plasma samples collected at surgery, 6 months, 1 year, and 3 years postoperatively, using gas/liquid chromatography and high-resolution mass spectrometry. We used meet-in-the-middle approach coupled with a series of metabolome-wide association analyses to identify overlapping metabolite associated with both DDE exposure and weight loss outcomes. Our findings revealed that DDE concentrations in visceral adipose tissue are associated with significant alterations in metabolites locally in adipose tissue pre-surgery and systemically in plasma post-surgery. Eight plasma metabolites were significantly associated with DDE exposure over time, while 27 were associated with BMI. Notably, methylbutyroylcarnitine was identified as a potential mediator, showing a positive association with both exposure and outcome. Eight adipose tissue metabolites were associated with both DDE and longitudinal changes in plasma metabolites, suggesting an indirect pathway linking DDE and weight changes.These findings enhance our understanding of DDE's obesogenic effect. The involved metabolic changes could attenuate the efficacy of bariatric surgery in achieving sustained weight loss, underscoring the importance of integrating environmental health considerations into clinical practice.