Serum Amyloid A3 Gene Expression in Adipocytes is an Indicator of the Interaction with Macrophages

Abstract

The infiltration of macrophages into adipose tissue and their interaction with adipocytes are essential for the chronic low-grade inflammation of obese adipose tissue. In this study, we identified the serum amyloid A3 (Saa3) gene as a key adipocyte-derived factor that is affected by interaction with macrophages. We showed that the Saa3 promoter in adipocytes actually responds to activated macrophages in a co-culture system. Decreasing C/EBPβ abundance in 3T3-L1 adipocytes or point mutation of C/EBPβ elements suppressed the increased promoter activity in response to activated macrophages, suggesting an essential role of C/EBPβ in Saa3 promoter activation. Bioluminescence based on Saa3 promoter activity in Saa3-luc mice was promoted in obese adipose tissue, showing that Saa3 promoter activity is most likely related to macrophage infiltration. This study suggests that the level of expression of the Saa3 gene could be utilized for the number of infiltrated macrophages in obese adipose tissue.

Adipocytes affect castration‐resistant prostate cancer cells to develop the resistance to cytotoxic action of NK cells with alterations of PD‐L1/NKG2D ligand levels in tumor cells

“…Therefore, further studies need to be done to reveal possible implications of other adipokines in such regulation. Especially, the role of adipokines that are reported to be involved in immune response (eg, adipsin, acylation stimulation protein [ASP], serum amyloid A3 [SAA3], and IL‐17D), should be investigated.…”

Transgenic mice specifically expressing amphiregulin in white adipose tissue showed less adipose tissue mass

“…In our previous reports, we isolated total RNAs from db / db and db /+ epididymal adipose tissues and compared the gene expression profiles by DNA microarray data analysis (Sanada et al., , ). Data analysis indicated that 1810 transcript levels were significantly up‐regulated in the adipose tissue of db / db mice ( p < .05).…”

“…DNA microarray analysis was performed in accordance with our previous study (Sanada et al., , ). Total RNA derived from epididymal fat of AREG and control mice at 8 weeks of age was isolated using RNeasy Lipid Tissue Mini Kit and subjected to cRNA synthesis for a DNA microarray analysis according to the manufacturer's instructions (whole mouse genome 60‐mer oligo microarray, Agilent Technologies, Santa Clara, CA).…”

“…Because we have recently performed a comparative analysis of gene expression in obese adipose tissues of db / db mice (Sanada et al., , ), we expected that these transcriptome data would be useful to isolate candidate genes related to aberrant cell proliferation. In this study, we isolated amphiregulin ( Areg ), which is highly expressed in obese white adipose tissue.…”

Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve

“…Clinical studies of viral infections in humans [ 5 , 8 , 9 ], including COVID-19 [ 10 ], suggest that SAA is a sensitive biomarker for early diagnostics and treatment and a predictor of the viral disease outcome. Mouse model studies report that SAA3 is a sensitive biomarker of excessive inflammation upon vaccination [ 11 ] and of macrophage infiltration of the adipose tissue in obesity [ 12 ]. Whether SAA is not just a marker but also an active participant in disease is intensely investigated, and numerous, sometimes conflicting, functions have been ascribed to this mysterious protein.…”