PT  - JOURNAL ARTICLE
AU  - Alicia R. Romero
AU  - Andre Mu
AU  - Janelle S. Ayres
TI  - Fat specific adipose triglyceride lipase is necessary for iron-mediated lipolysis and lipid mobilization in response to negative energy balance
AID  - 10.1101/2021.08.05.455308
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.05.455308
4099  - http://biorxiv.org/content/early/2021/08/06/2021.08.05.455308.short
4100  - http://biorxiv.org/content/early/2021/08/06/2021.08.05.455308.full
AB  - Maintenance of energy balance is essential for the overall health of an organism. In mammals, both negative and positive energy balance are associated with disease states. To maintain their energy balance within a defined homeostatic setpoint, 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. Using a dietary model, we found that a short course of excess dietary iron caused a negative energy balance resulting in a severe whole body wasting phenotype. This disruption in energy balance was due to an iron dependent increase in energy expenditure caused by a heightened basal metabolic rate and activity level. Using a transgenic mouse model lacking adipose triglyceride lipase (ATGL) specifically in fat tissue, we found that to meet the increased energetic demands, dietary iron caused increased lipid utilization that required fat specific ATGL-mediated lipid mobilization and wasting of subcutaneous white adipose tissue deposits. When fed dietary iron, mice lacking fat-specific ATGL activity were protected from fat wasting, and developed a severe cachectic response that is necessary to meet the increased energetic demands caused by the dietary regimen. Our work highlights the multi-faceted role of iron regulation of organismal metabolism and provides a novel in vivo mechanism for micronutrient control of lipolysis that is necessary for regulating mammalian energy balance.Competing Interest StatementThe authors have declared no competing interest.