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.
Highlights
Obesity, in particular excess visceral adiposity, and obesity-related metabolic disorders have emerged as crucial health issues worldwide
We carried out a comparative analysis based on these in vivo and in vitro transcriptomic data in order to identify in vivo adipocyte-derived genes that were possibly affected by infiltrated macrophages in obese adipose tissue (Fig. 1A)
These observations indicated that these three genes can be considered to be key adipocyte-derived factors whose expression is up-regulated by interaction with macrophages and potentially available as indicators of the number of macrophages in obese adipose tissue
Summary
In particular excess visceral adiposity, and obesity-related metabolic disorders have emerged as crucial health issues worldwide. Determination of the number of infiltrated macrophages and in vivo evaluation of their interaction with adipocytes are essential for assessment of the chronic inflammatory state in obese adipose tissue. We performed a comparative analysis on the gene expression of obese adipose tissue of db/db mice and with vitamin B6 supplementation Using this approach and by obtaining transcriptomic data, candidate genes related to the increase in infiltrated macrophages in adipose tissue in vivo were identified[20,22]. Because activated macrophages could spread systemically in obese mice, we focused on adipocyte-derived genes that are differentially regulated by interaction with activated macrophages in order to establish a new non-invasive in vivo model for evaluation of the adipose inflammatory state associated with macrophage infiltration. In vivo assessment of the chronic low-grade inflammatory state of obese fat by determining macrophage infiltration would be important to evaluate the preventive effect of pharmaceutical agents and functional food against obesity-related disorders
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