# Impaired Lipophagy and Lipid Droplet Accumulation in Osteoblasts

> **NIH NIH K01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $95,078

## Abstract

Dr. Elizabeth Rendina-Ruedy is currently a senior postdoctoral fellow at the Maine Medical Center Research
Institute in Dr. Clifford J. Rosen's laboratory. Her 13+ years of training and research has been deeply rooted in
bone biology with an emphasis in nutritional biochemistry. While the research strategy outlined in this
application will take advantage of these strengths and interests, a much more molecular, transdisciplinary
approach is proposed to determine the metabolic function of neutral lipid droplets in osteo-progenitor cells. As
such, Dr. Rendina-Ruedy's mentor team, Dr. Rosen and Dr. Michael P. Czech, epitomize the integration of the
two fields, while also providing impeccable support and guidance to the candidate during her transition to an
independent investigator. The applicant and her mentors have developed an individualized plan to include
structured activities that will significantly enhance her research career, including: considerable mentor-mentee
contact; enhancing research skills, methodologies, and expertise; involvement in courses, workshops, and
training sessions; and, the dissemination of research and knowledge. Additionally, MMCRI offers an
exceptional biomedical research environment, as well as supportive staff that are committed to promoting
young scientists. The research plan expands on preliminary findings made by Dr. Rendina-Ruedy during her
doctoral training, which demonstrated that bone-lining osteo-progenitor cells accumulated lipid droplets in a
diet-induced obese mouse model of type 2 diabetes mellitus (T2DM). These data also corresponded to lower
cancellous bone volume and a decrease in osteoblastogenesis. These data were of particular interest given
that the clinical manifestation of T2DM is associated with an increase in fracture risk, independent of bone
mineral density (BMD), along with a decrease in bone formation. Taken together, the hypotheses being tested
in the current application are that (1) intracellular lipid droplet lipolysis via lipophagy supports bone formation
by enhancing osteoblast differentiation through the generation and utilization of energy substrates; and (2)
bone formation is compromised in obesity-related metabolic derangements such as T2DM, due to impaired
lipophagy. These hypotheses will be addressed by integrating an innovative pulse-chase, co-localization
experiment (specific aim 1A), as well as determining metabolic fuel dependency and flexibility in bone marrow
stromal cells (specific aim 1B). Additionally, we will generate a novel conditional perilipin (Plin)-2 knock out,
targeted in osteo-progenitor cells (Prx1-Cre) as a means to protect from diet-induced obesity compromise in
bone by up-regulating lipid droplet lipolysis. In summary,
Dr. Rendina-Ruedy's proposed project, under the
mentorship of Drs. Rosen and Czech, represents a highly significant research problem in the field of bone
biology that will be investigated by integrating innovative lipid biology strategies. Ultim...

## Key facts

- **NIH application ID:** 9761431
- **Project number:** 5K01AR072123-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Elizabeth Rendina-Ruedy
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $95,078
- **Award type:** 5
- **Project period:** 2019-09-13 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9761431

## Citation

> US National Institutes of Health, RePORTER application 9761431, Impaired Lipophagy and Lipid Droplet Accumulation in Osteoblasts (5K01AR072123-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9761431. Licensed CC0.

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