Adipose triglyceride lipase mediates lipolysis and lipid mobilization in response to iron-mediated negative energy balance
Alicia R. Romero,
Andre Mu,
Janelle S. Ayres
Affiliations
Alicia R. Romero
Molecular and Systems Physiology Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Gene Expression Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Andre Mu
Molecular and Systems Physiology Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Gene Expression Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
Janelle S. Ayres
Molecular and Systems Physiology Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Gene Expression Lab, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Corresponding author
Summary: 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-specific ATGL deficiency protected mice from fat wasting, but caused a severe cachectic response in mice when fed iron. Our work reveals a mechanism for micronutrient control of lipolysis that is necessary for regulating mammalian energy balance.
