biostudies-literatureRomero ARKenneth Rainin FoundationNOMIS StiftungUniversity of California, San DiegoNCI NIH HHSNational Institutes of Health103941https://www.ebi.ac.uk/biostudies/studies/S-EPMC8899412biostudies-literatureUnknown25(3)Maintenance of energy balance is essential for overall organismal health. Mammals have evolved complex regulatory mechanisms that control energy intake and expenditure. Traditionally, studies have focused on understanding the role of macronutrient physiology in energy balance. In the present study, we examined the role of the essential micronutrient iron in regulating energy balance. We found that a short course of dietary iron caused a negative energy balance resulting in a severe whole body wasting phenotype. This disruption in energy balance was because of impaired intestinal nutrient absorption. In response to dietary iron-induced negative energy balance, adipose triglyceride lipase (ATGL) was necessary for wasting of subcutaneous white adipose tissue and lipid mobilization. Fat-specifiScienceAdipose triglyceride lipase mediates lipolysis and lipid mobilization in response to iron-mediated negative energy balance.PMC8899412DP1 AI144249P30 CA014195R01AI114929Romero ARAyres JSMu AfalseAdipose triglyceride lipase mediates lipolysis and lipid mobilization in response to iron-mediated negative energy balance.Maintenance of energy balance is essential for overall organismal health. Mammals have evolved complex regulatory mechanisms that control energy intake and expenditure. Traditionally, studies have focused on understanding the role of macronutrient physiology in energy balance. In the present study, we examined the role of the essential micronutrient iron in regulating energy balance. We found that a short course of dietary iron caused a negative energy balance resulting in a severe whole body wasting phenotype. This disruption in energy balance was because of impaired intestinal nutrient absorption. In response to dietary iron-induced negative energy balance, adipose triglyceride lipase (ATGL) was necessary for wasting of subcutaneous white adipose tissue and lipid mobilization. Fat-specif2022-01-01T00:00:00Z2022 Mar2025-04-04T09:00:34.284Z2025-04-04T09:00:34.284ZS-EPMC88994123526581310.1016/j.isci.2022.103941