| First Author | Ma YL | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 503 |
| Issue | 3 | Pages | 1651-1658 |
| PubMed ID | 30131248 | Mgi Jnum | J:271987 |
| Mgi Id | MGI:6276775 | Doi | 10.1016/j.bbrc.2018.07.095 |
| Citation | Ma YL, et al. (2018) Suppressing Irf2bp2 expressions accelerates metabolic syndrome-associated brain injury and hepatic dyslipidemia. Biochem Biophys Res Commun 503(3):1651-1658 |
| abstractText | Increasing studies indicate that high fat diet (HFD) induces neuroinflammation in animal models with obesity, yet the pathology of it is unclear. Interferon Regulatory Factor 2 Binding Protein 2 (Irf2bp2) is a key regulator of macrophage polarization, playing an essential role in regulating inflammatory response. This study investigated the effects of Irf2bp2 on HFD-induced brain injury, and explored the possible molecular mechanisms using wild type (WT) and Irf2bp2 knockout (KO) mice. The results indicated that HFD-increased body weight of mice was further elevated by Irf2bp2-knockout. In addition, Irf2bp2-deletion accelerated HFD-induced metabolic syndrome, as evidenced by the promoted fasting glucose and insulin levels. In the results of behavioral measurements, Irf2bp2-knockout intensified cognitive deficit in HFD-fed mice by using Y-maze, passive avoidance, and morris water maze (MWM) tests. Further, Irf2bp2-deficiency accelerated the activation of astrocytes and microglia cells, as evidenced by the promoted expressions of glial fibrillary acidic protein (GFAP) and Iba-1 in hippocampus and hypothalamus of HFD-fed mice. HFD for 16 weeks induced oxidative stress in serum and brain of mice, as proved by the up-regulated malondialdehyde (MDA) levels and down-regulated superoxide dismutase (SOD) activity, which were significantly enhanced due to Irf2bp2 knockout. Moreover, HFD-triggered systematic and central nervous inflammation by increasing the release of interleukin 1beta (IL-1beta) and tumor necrosis factor (TNF)-alpha, accompanied with elevated p-nuclear factor-kappaB (NF-kappaB) expressions. Notably, HFD-induced inflammation was significantly exacerbated by Irf2bp2 deletion. Intriguingly, HFD-induced dyslipidemia in liver of mice was further aggravated by Irf2bp2 suppression. Our in vitro results verified the effects of Irf2bp2-inhibition on the promotion of inflammatory response in BV2 cells and lipid dysfunction in primary hepatocytes. Therefore, the findings above suggested that inhibiting Irf2bp2 expression provided a potential therapeutic approach for the prevention of metabolic syndrome-associated central nervous injury. |
