Depot differences in adipokine secretion from human omental and abdominal subcutaneous adipose tissues: potential role of adiporedoxin
Knebusch Toriello, Stefanie
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Adiporedoxin (Adrx) is an adipose tissue specific protein discovered by the Pilch lab. It is a member of the peroxiredoxin family localized in the endoplasmic reticulum (ER). Previous studies showed that Adrx is involved in ER redox regulation and disulfide bond formation and secretion of adipokines. Further, Adrx mRNA expression and protein levels in human abdominal adipose tissue of young, healthy subjects, ranging in levels of obesity, correlated positively with adiponectin mRNA and protein, and negatively with adipose tissue inflammation (as indicated by phospho-Jun kinase). Since previous studies have shown depot differences in adipokine release, we wanted to determine the differences on adipose tissues depot in Adrx expression. However, there are no data on depot differences in Adrx expression and its association with changes in adipokine release in human adipose tissue. It is well known that omental adipose tissue is more inflamed, and reports on depot differences in adipokine release, especially adiponectin are inconsistent however leptin and IL-6 have being consistent. Adipokine release measured from adipose tissues reflects a more physiologic state and the characteristics of the subjects compared to cultured cells. Adiponectin is an insulin sensitizing protein, exclusively produced by mature adipocytes and highly secreted by adipose tissue. The native adiponectin exists as low molecular weight, middle-molecular weight and high molecular weight (HMW).The potency of adiponectin is linked to the HMW isoform. There are no previous reports on secretion of HMW adiponectin from human omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues. In this study the goal is to determine the depot differences in Adrx expression and adipokine release in human Abdsc and Om adipose tissue in obese and morbidly obese subjects, mostly females and to determine the relationship between Adrx protein expression and adipokine release in Abdsc versus Om and circulating levels of adipokines, primarily total and HMW adiponectin. To clarify whether Adrx expression is implicated in the release and secretion of circulating adipokines. Adrx protein levels (assessed by Western blot) were ~1.4 fold higher in Abdsc than Om (p<0.05; paired t-test values). As expected, secretion per gram of tissue in 3hr incubation of total adiponectin (~ 25%) and leptin (~50%) was higher, and IL-6 secretion was lower (~30%) in Abdsc compared to Om. In western blot, total adiponectin is higher in Abdsc compared to Om. However, HMW adiponectin and % HMW are higher in Om. Adrx protein levels were positively correlated with total adiponectin and HMW release in Abdsc and only with HMW in Om. Adrx levels were negatively correlated with % HMW in Abdsc but not in Om. Adrx protein levels in Abdsc showed a negative trend with total adiponectin circulating levels (ng/ml measured by ELISA) and a positive trend in Om. However, total adiponectin by Western Blot showed a positive trend with Adrx levels in both Abdsc and Om. HMW adiponectin levels tended to be slightly positive with Adrx levels in Abdsc and Om. However, the percent of HMW adiponectin levels are not correlated with Adrx levels in either tissues. Since in Adrx KO mice found that presented lower total adiponectin in circulation, it was hypothesized that Adrx were positively correlated with circulating adiponectin, and wanted to study the correlation with serum adipokines. However, none of the correlations with Adrx and adipokines in serum were statistically significant. These data suggest that depot differences in Adrx expression may influence depot differences in adipokine secretion. The mechanism of higher HMW adiponectin secretion in Om with low Adrx levels needs further study.