Pro‐inflammatory cytokines and glucose regulate expression of adiponectin receptors in porcine adipocytes

Abstract

The anti-inflammatory activity of adiponectin may contribute to its insulin sensitizing effects. Two adiponectin receptors have been identified as adipoR1 (R1) and adipoR2 (R2), and down regulation of these receptors may promote insulin resistance. The aim of this research was to determine if tumor necrosis factor α (TNFα), interleukin-6 (IL6), or hyper-glycemic conditions regulate receptor expression in adipocytes, and whether inhibition of the JAK-STAT pathway by AG490 alters this regulation. Primary adipocytes were prepared from subcutaneous adipose tissue of pigs (n=3). Cells were incubated ± TNFα or IL6 (30 ng/mL), with or without pretreatment of 10 μM AG490, in hyper-glycemic or normo-glycemic conditions for 6 h. Total RNA was extracted and gene expression determined by real time PCR. There was no effect of cytokines at 5.5 mM glucose for R1 expression. However, there was a trend for a down-regulation of R2 by AG490-TNFα (P < 0.07). At 25 mM glucose, there was a similar reduction in R1 by AG490-TNFα treatment (P = 0.06). R2 was marginally reduced by IL6, but there was a reduction (P < .01) with AG490+IL6. High glucose caused a reduction of both receptors, whereas TNFα increased both in the high glucose media. R1 (P < 0.1) and R2 (P < 0.05) were further elevated by AG490+TNFα in high glucose. Interestingly, IL6 and AG490+IL6 (P < 0.05) reduced R1 and R2 expression, but only in the high glucose media. Collectively, these data indicate that the effects of TNFα and IL6 on adiponectin receptor expression are influenced by glucose concentration, and that the JAK-STAT pathway may be a determinant of adiponectin receptor expression.