Effects of myeloid sirtuin 1 deficiency on hypothalamic neurogranin in mice fed a high-fat diet

Biochem Biophys Res Commun. 2019 Jan 1;508(1):123-129. doi: 10.1016/j.bbrc.2018.11.126. Epub 2018 Nov 22.


Hypothalamic inflammation has been known as a contributor to high-fat diet (HFD)-induced insulin resistance and obesity. Myeloid-specific sirtuin 1 (SIRT1) deletion aggravates insulin resistance and hypothalamic inflammation in HFD-fed mice. Neurogranin, a calmodulin-binding protein, is expressed in the hypothalamus. However, the effects of myeloid SIRT1 deletion on hypothalamic neurogranin has not been fully clarified. To investigate the effect of myeloid SIRT1 deletion on food intake and hypothalamic neurogranin expression, mice were fed a HFD for 20 weeks. Myeloid SIRT1 knockout (KO) mice exhibited higher food intake, weight gain, and lower expression of anorexigenic proopiomelanocortin in the arcuate nucleus than WT mice. In particular, KO mice had lower ventromedial hypothalamus (VMH)-specific neurogranin expression. However, SIRT1 deletion reduced HFD-induced hypothalamic neurogranin. Furthermore, hypothalamic phosphorylated AMPK and parvalbumin protein levels were also lower in HFD-fed KO mice than in HFD-fed WT mice. Thus, these findings suggest that myeloid SIRT1 deletion affects food intake through VMH-specific neurogranin-mediated AMPK signaling and hypothalamic inflammation in mice fed a HFD.

Keywords: Food intake; Hypothalamus; Neurogranin; Obesity; Sirtuin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Calcium Signaling
  • Diet, High-Fat / adverse effects
  • Eating
  • Gene Expression
  • Hypothalamus / metabolism*
  • Inflammation / metabolism
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / metabolism*
  • Neurogranin / metabolism*
  • Pro-Opiomelanocortin / metabolism
  • Sirtuin 1 / deficiency*
  • Sirtuin 1 / genetics
  • Ventromedial Hypothalamic Nucleus / metabolism


  • Nrgn protein, mouse
  • Neurogranin
  • Pro-Opiomelanocortin
  • Sirt1 protein, mouse
  • Sirtuin 1