Secreted Phosphoprotein 1 (SPP1) Modulates Intracellular Metabolic Programs in Mature Adipocytes Revealed by...

Area of Science:

• Metabolomics
• Adipose Tissue Biology
• Molecular Endocrinology

Background:

• Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is a key factor in adipose tissue inflammation and remodeling.
• Understanding SPP1's role in adipocyte metabolism is crucial for metabolic disease research.

Purpose of the Study:

• To investigate the dose-dependent effects of SPP1 on the metabolic profiles of differentiated 3T3-L1 adipocytes.
• To identify specific metabolic pathways modulated by SPP1 in adipocytes.

Main Methods:

• Untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was employed.
• Differentiated 3T3-L1 adipocytes were treated with varying concentrations of SPP1 (100 ng/mL and 500 ng/mL).
• Multivariate statistical analyses (PCA, PLS-DA, sparse PLS-DA) and pathway enrichment analysis were performed.

Main Results:

• Low-dose SPP1 (100 ng/mL) induced more pronounced intracellular metabolic remodeling compared to high-dose SPP1 (500 ng/mL).
• Distinct metabolic profiles were observed, with low-dose SPP1 altering carbohydrate and amino acid metabolism (e.g., pentose phosphate pathway).
• High-dose SPP1 selectively induced matrix metalloproteinase-12 (MMP-12), suggesting remodeling-associated responses.

Conclusions:

• SPP1 acts as a dose-dependent modulator of metabolic programs in mature adipocytes.
• SPP1 influences intracellular metabolic remodeling and can trigger specific remodeling-associated responses at higher concentrations.