Beyond the Surface: Mapping DDE's Metabolic Footprint on Adolescent Obesity

Zhenjiang Li; Shudi Pan; Brittney O Baumert; Jiawen Carmen Chen; Jesse A Goodrich; Hongxu Wang; Sarah Rock; Justin Ryder; Damaskini Valvi; Todd Jenkins; Stephanie Sisley; Xiangping Lin; Scott M Bartell; Thomas H Inge; Stavra Xanthakos; Brooklynn McNeil; Anna R Robuck; Catherine E Mullins; Sandrah P Eckel; Rob S McConnell; Michele A La Merrill; Douglas I Walker; David V Conti; Lida Chatzi

doi:10.1289/EHP16341

Beyond the Surface: Mapping DDE's Metabolic Footprint on Adolescent Obesity

Environ Health Perspect. 2025 Jun 3. doi: 10.1289/EHP16341. Online ahead of print.

Authors

Zhenjiang Li¹, Shudi Pan¹, Brittney O Baumert¹, Jiawen Carmen Chen¹, Jesse A Goodrich¹, Hongxu Wang¹, Sarah Rock¹, Justin Ryder², Damaskini Valvi³, Todd Jenkins⁴, Stephanie Sisley⁵, Xiangping Lin⁶, Scott M Bartell⁷, Thomas H Inge², Stavra Xanthakos⁸, Brooklynn McNeil⁹, Anna R Robuck¹⁰, Catherine E Mullins¹¹, Sandrah P Eckel¹, Rob S McConnell¹, Michele A La Merrill¹², Douglas I Walker¹¹, David V Conti¹, Lida Chatzi¹

Affiliations

¹ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Department of Surgery, Northwestern University Feinberg School of Medicine and Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
³ Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinatti, OH, USA.
⁵ USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁶ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Environmental and Occupational Health, Department of Epidemiology and Biostatistics, and Department of Statistics, University of California, Irvine, CA, USA.
⁸ Division of Gastroenterology, Hepatology, Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinatti, OH, USA.
⁹ Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.
¹⁰ Graduate School of Oceanography, University of Rhode Island, Narragansett, RI, USA.
¹¹ Gangarosa Department of Environmental Health, Emory University, Atlanta, GA, USA.
¹² Department of Environmental Toxicology, University of California, Davis, CA, USA.

PMID: 40460320
DOI: 10.1289/EHP16341

Abstract

Background: 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.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: 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.

Results: 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.

Discussion: 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. https://doi.org/10.1289/EHP16341.