Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets

Biochem Biophys Res Commun. 2018 May 23;499(4):1025-1031. doi: 10.1016/j.bbrc.2018.04.044. Epub 2018 Apr 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Body Weight
  • Diet, High-Fat
  • Feeding Behavior*
  • Hippocampus / pathology*
  • Inflammation / pathology*
  • Insulin Resistance
  • Lipocalin-2 / blood
  • Macrophages / metabolism
  • Mice, Knockout
  • Myeloid Cells / metabolism*
  • Sirtuin 1 / deficiency*
  • Sirtuin 1 / metabolism


  • Lipocalin-2
  • Lcn2 protein, mouse
  • Sirtuin 1