Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Brody School of Medicine East Carolina University Greenville NC 27834 USA

Center for Environmental Health Sciences Mississippi State University Mississippi State MS 39762 USA

Clinical Epidemiology Department of Medical Sciences Uppsala University Hospital Uppsala University Uppsala Sweden

College of Health and Medicine Australian National University Canberra Australia

College of Pharmacy Texas A and M University College Station TX 77843 USA

Department of Animal Science School of Environmental and Biological Science Rutgers University New Brunswick NJ 08901 USA

Department of Biochemistry University of Paris INSERM T3S 75006 Paris France

Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences Brno Czech Republic

Department of Developmental and Cell Biology University of California Irvine Irvine CA 92697 USA

Department of Endocrinology University of Bari Aldo Moro Bari Italy

Department of Environmental and Occupational Health Sciences School of Public Health SUNY Downstate Health Sciences University Brooklyn NY 11203 USA

Department of Epidemiology The University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA

Department of Life and Health Sciences University of Bordeaux INSERM Pessac France

Department of Physiology and Pharmacology Karolinska Institute Solna Sweden

Department of Preventive Medicine and Public Health University of Granada Granada Spain

Department of Systems Biology and Bioinformatics University of Paris INSERM T3S Paris France

Division of Biological Sciences The University of Missouri Columbia MO 65211 USA

Division of Endocrinology Department of Pediatrics University of California San Francisco CA 94143 USA

Division of Endocrinology Diabetes and Metabolism The University of Illinois at Chicago Chicago Il 60612 USA

Division of Gastroenterology Hepatology and Nutrition University of Louisville Louisville KY 40402 USA

Environmental Health and Disease Laboratory University of South Carolina Columbia SC 29208 USA

Health and Environment Research Lab The Azrieli Faculty of Medicine Bar Ilan University Israel

Healthy Environment and Endocrine Disruptor Strategies Commonweal Bolinas CA 92924 USA

Institute of Environmental Health Sciences and Department of Pharmacology Wayne State University Detroit MI 48202 USA

McMaster University Department of Obstetrics and Gynecology Hamilton Ontario CA USA

Norris Cotton Cancer Center Department of Molecular and Systems Biology Geisel School of Medicine at Dartmouth Lebanon NH 03756 USA

Obstetrics and Gynecology University of Cote d'Azur Cote d'Azur France

Occupational and Environmental Health Research Group University of Stirling Stirling Scotland

Occupational and Environmental Medicine Department of Medical Sciences Uppsala University Hospital Uppsala University Uppsala Sweden

Sorbonne Paris Nord University Bobigny INSERM U1124 Paris France

The Institute for Global Food Security School of Biological Sciences Queen's University Belfast Northern Ireland UK

Univ Rennes INSERM EHESP IRSET UMR_5S 1085 35000 Rennes France

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Biochem Pharmacol. 2022 Aug;202:115144. doi: 10.1016/j.bcp.2022.115144. PubMed

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