Abstract 1587: Interleukin-10-Induced Adiponectin Production in Adipogenic Visceral Stromal-Vascular Cells
Background: Inflammation plays important roles in the pathogenesis of metabolic syndrome. We reported that interleukin (IL)-10, an anti-inflammatory cytokine, ameliorated dyslipidemia and hypertension in rodents. Although IL-10 might preferably modulate metabolic factors, direct effects of IL-10 on adipocytes remain unknown. Here we investigated the effects of IL-10 on adipocytokine production and adipogenic differentiation using visceral stromal-vascular cell (SVC), a progenitor of adipocyte.
Methods and Results: Primary SVCs from the rat mesenterium were incubated with media containing natural lipids for adipogenic differentiation, but not containing indomethacin, dexamethazon, and PPARγ agonists, to simulate condition of metabolic syndrome in vitro. We measured adipocytokine concentrations in culture supernatants by ELISA, and PPARγ gene expression by real-time RT-PCR. (Study 1) To examine the effects on adipogenic differentiation, we stimulated SVCs with IL-10 (10–100 ng/ml) from Day 0 to 6. Oil red O staining at Day 7 showed that IL-10 produced smaller lipid particles in adipocytes, without increasing the intracellular lipid amounts quantified with OD540 nm measurement. In contrast, continuous IL-10 stimulation caused about 2.2-fold increase of adiponectin secretion and 3.4-fold increase of PPARγ gene expression at Day 6. (Study 2) To examine the effects on mature adipocytes, we added IL-10 into culture media at Day 6.
Addition of IL-10 increased adiponectin secretion in a time (0–24 h)- and dose (1–100 ng/ml)-dependent manner (IL-10 vs. control at 24 h, 794.4 ± 90.1 vs. 504.1 ± 40.2 ng/ml, P<0.05, n=4). PPARγ expression was not enhanced along with the increase of adiponectin levels. Moreover, pretreatment with a PI3 kinase inhibitor wortmannin, but not a PPARγ antagonist GW9662, significantly inhibited the IL-10-induced adiponectin production. In contrast, IL-10 did not alter leptin and TNF-α levels compared to controls (238.4 ± 8.6 vs. 223.1 ± 0.8 pg/ml, 396.8 ± 18.2 vs. 407.0 ± 21.8 pg/ml, respectively).
Conclusion: IL-10 enhanced adiponectin production and PPARγ expression without promoting adipogenic differentiation in visceral SVCs. These results suggest the potential for therapeutic use of IL-10 in metabolic syndrome.