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Investigating the impact of abnormal lipid metabolism on mouse intervertebral disc

Award Number: K99AR085178
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/05/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Investigating the impact of abnormal lipid metabolism on mouse intervertebral disc - Project Summary/Abstract Hyperlipidemia, i.e. elevated serum lipids, has been identified as a risk factor for intervertebral disc (IVD) degeneration (IDD), but the underlying mechanism remains elusive. Epidemiologic studies have suggested mechanisms underlying hyperlipidemia and IDD other than obesity-induced mechanical stress, suggesting that elevated lipids may directly affect metabolic homeostasis in the IVD. However, oxygen demanding lipid metabolism has been considered minimal in hypoxic IVD, which has impeded investigation of this possibility thus far. Our preliminary data have uncovered an active lipid metabolism in mouse IVDs: they take up systemic lipids, undergo fatty acid oxidation (FAO) and store them in lipid droplets (LD). Furthermore, when lipid metabolism is disrupted by blocking FAO in a genetic mouse model or by lipid overload in a high-fat diet (HFD)-induced hyperlipidemia model, we observed significant lipid accumulation in nucleus pulposus (NP) cells. Histological evaluation revealed that in addition to abnormal lipid accumulation, there was a significant decrease in disc height and proteoglycan content in the NP in the HFD model. Biomechanical tests revealed a compromised mechanical strength of the IVDs from HFD-fed mice. In humans, the primary functional role of the IVD is to provide mechanical support to the spine. Reductions in proteoglycan content, disc height, and mechanical strength are early signs of IDD and can lead to severe IDD later in life. To investigate whether the early IDD changes caused by abnormal lipid metabolism can progress to severe IDD in the mouse models whose IVDs are not weight-bearing, we aim to comprehensively assess the mechanical properties of the intervertebral disc using an in vivo spinal instability-induced IDD mouse model in addition to the ex vivo testing system. In addition, we will establish a spatial lipidomics approach (Mass Spectrometry Imaging) and single- cell RNA sequencing in this training program to study metabolic changes and cellular responses to abnormal lipid metabolism in mouse models. We will also evaluate back pain-like behaviors in these animal models. The results of this project will reveal a novel mechanistic link between hyperlipidemia and IDD and lay the foundation for future studies exploring diagnostic/prophylactic/therapeutic approaches for lipid-related spine diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $115,301 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/20/2026	NON-COMPETING CONTINUATION	$115,301
2026	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/21/2026	NEW	$0
														Subtotal = $115,301

Issue Date FY: 2025 ( Subtotal = $115,301 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/4/2025	NEW	$115,301
														Subtotal = $115,301

Grand Total All Awards = $230,602

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Investigating the impact of abnormal lipid metabolism on mouse intervertebral disc

Award Number: K99AR085178

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/05/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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