Loss of microglial PTP1B mitigates neuroinflammation and cognitive deficits induced by obesity

Long-term intake of high-fat diet (HFD) can impair cognitive function, which emerges as a risk factor for neurodegenerative diseases. Tyrosine protein kinase 1B (PTP1B) is reported to be associated with inflammation and cognitive impairment. However, the role of PTP1B in HFD-induced cognitive deficits remains elusive. Here, we demonstrate that PTP1B in microglia is essential for neuroinflammation and cognitive deficits induced by HFD. To model the specific deficiency of PTP1B in microglia, we crossed mice with loxP-flanked PTP1B (PTP1Bfl/fl) with Cx3cr1-Cre mice to generate Cx3cr1-Cre:PTP1Bfl/fl mice, and then induced the knockout of microglial Ptp1b via administrating Tamoxifen (the mice were hereinafter referred to as Cx3cr1-Ptp1b-/-). Their Cre-negative littermates after treating with Tamoxifen were used as controls (Ptp1bfl/fl; hereafter referred to as controls, Con). To further understand molecular mechanisms involved in microglial PTP1B loss preventing HFD-induced cognitive impairment, we performed RNA sequencing to reveal the global gene expression profile in the hippocampus.