Chronic low-grade inflammation-induced insulin resistance is associated with neuroinflammation. Myeloid sirtuin1 (SIRT1) deficiency aggravates high-fat diet (HFD)-induced insulin resistance. However, the function of myeloid-specific SIRT1 in the hippocampus of obese mice is largely unknown. To address this question, we fed myeloid SIRT1 knockout (KO) mice a HFD for 40 weeks. We found that HFD-fed SIRT1 KO mice had increased insulin resistance and macrophage infiltration in adipose tissue than wild type (WT) mice. Levels of HFD-induced lipocalin-2 (LCN2) were lower in SIRT1 KO mice than in WT. HFD-induced hippocampal LCN2 expression was lower in HFD-fed SIRT1 KO mice than in WT. Hippocampal acetylation of nuclear factor-κB (NF-κB) and amyloid precursor protein levels were higher in HFD-fed SIRT1 KO mice than in HFD-fed WT mice. Taken together, our results suggest that targeted induction of the anti-inflammatory effects of SIRT1 and LCN2 may help prevent obesity-associated insulin resistance and neuroinflammation.
Keywords: Hippocampus; Inflammation; Insulin resistance; Lipocalin-2; Obesity; SIRT1.
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