Suppressing Irf2bp2 expressions accelerates metabolic syndrome-associated brain injury and hepatic dyslipidemia
- Department of Anesthesiology, Ankang Central Hospital, Ankang, 725000 (China)
- Department of Anesthesiology, Ankang Municipality Maternity and Child Care, Ankang, 725000 (China)
- Intensive Care Unit, HongHui Hospital of Xi'an Jiaotong University, Xi'an, 710000 (China)
Highlights: • Irf2bp2 deletion promotes HFD-induced metabolic syndrome and cognitive dysfunction in mice. • Irf2bp2 knockout aggravates brain injury in HFD-fed mice. • Irf2bp2 ablation alleviates oxidative stress and inflammation in brain of HFD-fed mice. • Suppressing Irf2bp2 expressions exacerbate inflammatory response in PAL- or LPS-treated BV2 cells. 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 1β (IL-1β) and tumor necrosis factor (TNF)-α, accompanied with elevated p-nuclear factor-κB (NF-κB) 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.
- OSTI ID:
- 23103680
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 3; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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