The Arkansas Integrative Metabolic Research Center will host Neha Dole, an assistant professor in the departments of Physiology and Cell Biology, Orthopaedic Surgery and Pediatrics at the University of Arkansas for Medical Sciences, at 12:55 p.m. on Wednesday, April 9, in ARKV 0002. Dole will discuss how the LCN2 axis regulates both energy balance and skeletal integrity and how understanding this axis offers new insight and novel targets for treating metabolic diseases and osteoporosis.

Abstract: The skeleton functions as an endocrine organ, actively influencing systemic metabolism. This talk explores the TGF-β-Lipocalin-2 (LCN2) axis as a critical bone-derived pathway that regulates both energy balance and skeletal integrity. TGF-β, a key modulator of bone remodeling, inversely regulates LCN2 expression in osteocytes. LCN2 acts endocrinologically to suppress appetite and improve insulin sensitivity via hypothalamic signaling. Locally, it promotes iron uptake through the SLC22A17 receptor, leading to iron overload, mitochondrial dysfunction and ferroptosis in bone cells. Additionally, LCN2 increases DKK1 and SOST expression, suppressing Wnt/β-catenin signaling and inhibiting osteoblast-driven bone formation. These findings reveal a dual role for LCN2 in regulating systemic metabolism and local bone health. Understanding this bone-origin signaling axis offers new insight into the intersection of skeletal biology, iron metabolism and energy homeostasis, highlighting novel targets for treating metabolic diseases and osteoporosis.

Biography: Neha Dole is an assistant professor at the University of Arkansas for Medical Sciences in the Departments of Physiology and Cell Biology, Orthopaedic Surgery and Pediatrics. Her research examines how obesity, weight loss and micronutrient status — especially iron — impact bone health and contribute to skeletal disorders such as osteoporosis and osteoarthritis. Focusing on pediatric and early-life influences, her lab studies how nutritional and metabolic factors shape bone development and systemic metabolism. The Dole Lab utilizes animal models and in vitro systems to explore bone energetics, mitochondrial dynamics and molecular responses to chronic metabolic stress. Techniques employed include micro-CT, histology, genomics, proteomics and biomechanical testing. A primary goal is to understand how the skeleton interacts with metabolic systems and to establish bone as a foundation for enhancing physical function and quality of life. Dole is funded by the NIH and DOD and actively mentors future scientists through leadership roles in national research organizations.

This event is supported by NIGMS of the National Institutes of Health under award number P20GM139768. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Pizza and beverages will be served. Please contact Kimberley Fuller, fullerk@uark.edu, for more information.

For those unable to attend in person, this seminar will also be available via Zoom.