| First Author | Ahmad F | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 28056 | PubMed ID | 27321128 |
| Mgi Jnum | J:266754 | Mgi Id | MGI:6218348 |
| Doi | 10.1038/srep28056 | Citation | Ahmad F, et al. (2016) Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue. Sci Rep 6:28056 |
| abstractText | Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance, and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1beta, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFalpha, IL1beta and proinflammatory genes. Following IP injection of lipopolysaccharide (LPS), serum levels of IL1beta and TNFalpha were reduced in PDE3B(-/-)mice compared to WT. Activation of signaling cascades, which mediate inflammasome responses, were modulated in PDE3B(-/-)mice WAT, including smad, NFAT, NFkB, and MAP kinases. Moreover, expression of chemokine CCL2, MCP-1 and its receptor CCR2, which play an important role in macrophage chemotaxis, were reduced in WAT of PDE3B(-/-)mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE(-/-)/PDE3B(-/-)and LDL-R(-/-)/PDE3B(-/-)mice compared to apoE(-/-)and LDL-R(-/-)mice, respectively. Obesity-induced changes in serum-cholesterol were blocked in PDE3B(-/-)mice. Collectively, these data establish a role for PDE3B in modulating inflammatory response, which may contribute to a reduced inflammatory state in adipose tissue. |
