Role of Adipocyte Na,K-ATPase Oxidant Amplification Loop in Cognitive Decline and Neurodegeneration - Expression profiling in Brain

Adipocyte-specific expression of Na,K-ATPase signaling antagonist, NaKtide, has been shown to ameliorate the pathophysiological consequences of obesity and improve diseased phenotype. Recent studies have established that the release of adipocytokines and other bioactive mediators in obesity contributes to neurodegeneration. This study utilizes a mechanistic approach and characterizes the hippocampal transcriptome in comparison with transcriptomic changes in liver, visceral and subcutaneous adipose tissue. RNAseq analysis in high fat diet fed transgenic mice showed large scale differential gene expression as well as modulation of several biological pathways in hippocampus, liver, visceral and subcutaneous adipose tissue, which were attenuated by doxycycline induced adipocyte specific NaKtide expression. Overall design: A total of 12 experimental conditions (three tissues: Liver, Visceral Adipose Tissue, and Subcutaneous Adipose Tissue; two diets: control diet and western diet; and two treatments: NaKtide and control) were compared. Five mice were placed in each experimental group for a total of 60 samples. Total RNA was extracted and used for expression profiing by RNA-Seq in a 2x50bp paired-end design.