Fish oil attenuates the expression of the CCL2 chemokine and histone-modifying enzymes in LPS-stimulated human preadipocytes.

In obesity, C-C chemokine ligand 2 (CCL2) plays a critical role in recruiting macrophages to white adipose tissue (WAT), contributing to chronic inflammation. In this study, we sought to explore the effects of fish oil (FO) on CCL2 expression and histone (H3K27)-modifying enzymes in both human model of preadipocytes and primary adipose-derived stem cells (ASCs). Present findings in preadipocytes lineage evidenced that lipopolysaccharide (LPS) increased TNF-alpha (∼5.8-fold) and CCL2 (∼3.8-fold) expression, modulating H3K27 modifying enzymes expression, including KDM6B and EP300. FO, in turn, significantly attenuated LPS-induced CCL2 expression and secretion and downregulated KDM6B and EP300, elucidating an important mechanism of action involved in the anti-inflammatory role of FO. We next isolated mature hypertrophied adipocytes from patient with overweight and exposed to LPS, resulting in increased CCL2/MCP-1 (∼3.8-fold) and TNF-alpha (∼4.5-fold) expression, effects significantly attenuated by FO. We also generated adipocyte-conditioned medium (ACM) and exposed ASCs to LPS or ACM for up to 72 h to assess CCL2/MCP-1 secretion. ACM from hypertrophied adipocytes stimulated increased CCL2/MCP-1 expression, which was partially reduced by FO. LPS treatment of primary ASCs led to a marked increase in CCL2 secretion, which was completely abolished by FO after 6 h, highlighting its potent anti-inflammatory effect. After 72 h, FO consistently maintained lower levels of CCL2, even during sustained inflammatory stimulation, underscoring its ability to modulate chronic inflammation. Additionally, the inhibition of NF-κB with JSH-23 mimicked the effects of FO on CCL2 expression, further suggesting that the anti-inflammatory actions of FO may involve NF-κB signaling. In conclusion, FO attenuates CCL2 expression and secretion in both preadipocytes and ASCs, providing evidence of its potential in modulating inflammation in WAT progenitor cells by modulating histone-modifying enzymes and inflammatory pathways.