Performing Department
Animal and Avian Sciences
Non Technical Summary
Iron is an essential mineral necessary for sustaining life, yet it becomes toxic when misplaced or accumulated in excess. Proper acquisition, distribution, and utilization of iron, along with the regulation of iron metabolism, are crucial for maintaining normal human and animal health. This project aims to uncover new mechanistic insights into how iron supports adipose function, potentially offering a foundation for understanding the link between iron deficiency and various metabolic pathologies, including obesity and diabetes.
Animal Health Component
10%
Research Effort Categories
Basic
90%
Applied
10%
Developmental
(N/A)
Goals / Objectives
Iron (Fe) is an essential micronutrient vital for growth and development in animals, with deficiency leading to health issues such as anemia and impaired thermogenesis. Adipose tissue, previously viewed as a lipid storage organ, is now recognized as an active metabolic tissue involved in energy balance. This research focuses on the role of Fe and transferrin receptor 1 (TfR1) in the beiging of white adipose tissue, where it transforms into energy-dissipating beige adipose tissue in response to factors like cold exposure and β3-adrenergic receptor (β3-AR) stimulation. Our preliminary data suggest that Fe is critical for cyclic adenosine monophosphate (cAMP) production via adenylyl cyclase 3 (AC3) in adipocytes, revealing a novel link between Fe metabolism and β3-AR-mediated signaling in adipocytes. Additionally, adipose-specific TfR1 knockout mice exhibit significant loss of inguinal white adipose tissue mass, indicating a crucial role for Fe during development. We will explore the mechanisms by which Fe and TfR1 influence thermogenic activation and adipose tissue maintenance. This research aims to provide insights into the interaction between Fe metabolism and adipocyte function, with implications for metabolic health in both animals and humans.
Project Methods
1. Molecular mapping the promoter regions responsible for Fe-responsive Adcy3-at transcription to identify the relevant transcription factor(s).2. Performing ChIP-seq (and ChIP-PCR) targeting H3K4me3 and H3K9me3, which are major targets of these Fe-requiring histone demethylases.3. Transcriptomic analysis in iWAT of TfR1-adi/adi and TfR1-floxed control mice.4. Establishing a TfR1 knockout iWAT cell culture model for further mechanistic investigation.