Adipocytes regulate monocyte development through the OGT-NEFA-CD36/FABP4 pathway in high-fat diet-induced obesity

Area of Science:

• Metabolic regulation of hematopoiesis
• Adipocyte biology and immune function

Background:

• Obesity, characterized by excessive adipocyte accumulation, is a major risk factor for numerous diseases.
• The impact of obesity on hematopoietic stem cell (HSC) function and differentiation is not fully understood.
• O-GlcNAc transferase (OGT) functions as a metabolic sensor regulating physiological processes.

Purpose of the Study:

• To investigate the role of adipocyte O-GlcNAc transferase (OGT) in monocyte development during obesity.
• To elucidate the mechanisms by which adipocyte OGT influences HSC differentiation in obesity.

Main Methods:

• Utilized a high-fat diet (HFD) induced obesity model in mice.
• Assessed peripheral monocyte levels and serum nonesterified fatty acids (NEFA).
• Investigated the expression and function of OGT in adipocytes and HSCs, including the NEFA-CD36/FABP4 pathway.

Main Results:

• Obesity correlated with elevated peripheral monocyte counts.
• Adipocyte OGT was essential for monocyte development in HFD-induced obesity, increasing monocytes via NEFA transcriptional activation.
• Loss of adipocyte OGT reduced serum NEFA, white adipose tissue, and inhibited HSC differentiation into monocytes in HFD-induced obesity.
• The NEFA-cluster of differentiation 36/fatty acid binding protein 4 (CD36/FABP4) pathway in HSCs was implicated in mediating OGT's effect on monocyte development.

Conclusions:

• Adipocyte OGT plays a critical role in maintaining hematopoietic homeostasis during obesity.
• Adipocyte OGT regulates monocyte development through NEFA signaling pathways, influencing HSC differentiation.