Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer's model mice

Kyong Nyon Nam, Anais Mounier, Cody M. Wolfe, Nicholas F. Fitz, Alexis Y. Carter, Emilie L. Castranio, Hafsa I. Kamboh, Valerie L. Reeves, Jianing Wang, Xianlin Han, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND). RNA-seq results revealed that in HFD mice there was an increased expression of genes related to immune response, such as Trem2 and Tyrobp. We found a significant increase of TREM2 immunoreactivity in the cortex in response to HFD, most pronounced in female mice that correlated to the amyloid pathology. Down-regulated by HFD were genes related to neuron projections and synaptic transmission in agreement to the significantly deteriorated neurite morphology and cognition in these mice. To examine the effect of the diet on the brain lipidome, we performed Shotgun Lipidomics. While there was no difference in the total amounts of phospholipids of each class, we revealed that the levels of 24 lipid sub-species in the brain were significantly modulated by HFD. Network visualization of correlated lipids demonstrated overall imbalance with most prominent effect on cardiolipin molecular sub-species. This integrative approach demonstrates that HFD elicits a complex response at molecular, cellular and system levels in the CNS.

Original languageEnglish (US)
Article number4307
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • General


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