Long-Term High-Fat Diet Affected Bone Marrow Microenvironment During Aging at Single-Cell Resolution.

Area of Science:

• Biomedical Science
• Aging Research
• Metabolic Disease

Background:

• Obesity, driven by high-fat diet (HFD), and aging are significant risk factors for chronic diseases.
• Understanding the impact of long-term HFD on aging (LHA) is crucial for developing interventions.

Purpose of the Study:

• To investigate the effects of LHA on the bone marrow microenvironment and solid organs.
• To identify molecular mechanisms linking LHA to pathology and inflammation.

Main Methods:

• Establishment of a long-term HFD to aging (LHA) mice model.
• Single-cell transcriptomics analysis of bone marrow cells.
• Analysis of gene expression, including Chil3 and Fabp4 in macrophages.

Main Results:

• LHA induced a shift from osteogenesis to adipogenesis in bone marrow.
• LHA altered immune cell populations and their metabolic adaptations.
• Upregulation of Chil3 and Fabp4 in bone marrow macrophages observed.
• Identified potential crosstalk axes (Ptn-Sdc3, Cxcl12-Cxcr4) between bone marrow and brain.

Conclusions:

• The bone marrow microenvironment is a central hub for LHA-induced pathology.
• Adipogenic reprogramming and myeloid cell dysfunction drive inflammation in LHA.
• Targeting the bone marrow offers therapeutic potential for obesity-accelerated aging.