Role of Adipocyte Na,K-ATPase Oxidant Amplification Loop in Cognitive Decline and Neurodegeneration - Expression profiling in Brain
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ABSTRACT: 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.
Project description: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.
Project description:The aim of this study was to characterize expression profiles of visceral and subcutaneous adipose tissue in children. Adipose tissue samples were collected from children having elective surgery (n=71, [54 boys], 6.0 +- 4.3 years). Affymetrix microarrays (n=20) were performed to characterize the functional profile and identify genes of interest in adipose tissue. Visceral adipose tissue had an overrepresentation of Gene Ontology themes related to immune and inflammatory responses and subcutaneous adipose tissue had an overrepresentation of themes related to adipocyte growth and development. Likewise, qPCR performed in the whole cohort showed a 30-fold increase in haptoglobin (P < 0.005), 7-fold increase in IL-10 (P < 0.001), 8-fold decrease in VEGF (P < 0.01) and a 28-fold decrease in TBOX15 (P < 0.001) in visceral compared to subcutaneous adipose tissue.The inflammatory pattern in visceral adipose tissue may represent an early stage of the adverse effects of this depot, and combined with chronic obesity, may contribute to increased metabolic and cardiovascular risk. 20 human samples from pre-pubertal boys and girls were assessed for differences in expression between subcutaneous (n=15) and visceral fat (n=5), with 1 microarray per subject
Project description:Distinct characteristics of adipose tissue at different localization of human body has shown greater significance in development of metabolic disorders. Visceral adipose tissue in particular is known to be associated with obesity related metabolic complications that include type II diabetes. In this experiment, we attempt to profile transcriptome signatures of adipocyte, stromal vascular fraction (SVF) and adipose tissue from subcutaneous and visceral adipose tissue from obese individuals.
Project description:The aim of this study was to characterize expression profiles of visceral and subcutaneous adipose tissue in children. Adipose tissue samples were collected from children having elective surgery (n=71, [54 boys], 6.0 +- 4.3 years). Affymetrix microarrays (n=20) were performed to characterize the functional profile and identify genes of interest in adipose tissue. Visceral adipose tissue had an overrepresentation of Gene Ontology themes related to immune and inflammatory responses and subcutaneous adipose tissue had an overrepresentation of themes related to adipocyte growth and development. Likewise, qPCR performed in the whole cohort showed a 30-fold increase in haptoglobin (P < 0.005), 7-fold increase in IL-10 (P < 0.001), 8-fold decrease in VEGF (P < 0.01) and a 28-fold decrease in TBOX15 (P < 0.001) in visceral compared to subcutaneous adipose tissue.The inflammatory pattern in visceral adipose tissue may represent an early stage of the adverse effects of this depot, and combined with chronic obesity, may contribute to increased metabolic and cardiovascular risk.
Project description:94 human adipocyte samples isolated from whole adipose tissues using collagenase digestion of tissue and flotation of lipid-laden adipocytes, followed by RNA isolation and RNA sequencing (SMARTer Stranded Total RNA-Seq library preparation, HiSeq 4000 100-bp paired-end reads). Adipocyte samples comprise subcutaneous and visceral adipocytes isolated from obese and lean people (N=24 obese-subcutaneous, N=24 obese-visceral, N=22 control-subcutaneous, N=24 control-visceral). Human adipocyte RNA sequencing data are provided as BAM files.
Project description:HFD feeding induces a rapid adipocyte progenitors (APs) proliferation in visceral adipose tissue (vWAT), followed by a block of differentiation. In contrast, subcutaneous adipose tissue (scWAT), in obesity, undergoes trans-differentiation of beige adipocytes to white and, consequently, a hyperplastic growth at later stages. We performed RNA-seq to investigate the global transcriptomic changes induced by HFD feeding
Project description:Diabetes and obesity are widespread diseases with signifciant socioeconomic implications. We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients. In this dataset, we include the expression data obtained from three types of adipose tissue; epigastric, subcutaneous, and visceral all obtained through open gastric bypass surgery. 18 total samples were analyzed. Tissues were paired together to run on one genechip, with three pairs of epigastric, three pairs of subcutaneous, and three pairs of visceral were ran on nine genechips. Comparisons of gene expression in the form of fold changes between pairs of adipose types (i.e., subcutaneous/epigastric, visceral/epigastric, and subcutaneous/visceral) were completed by Spotfire Analysis.
Project description:HFD feeding induces a rapid adipocyte progenitors (APs) proliferation in visceral adipose tissue (vWAT), followed by a block of differentiation. In contrast, subcutaneous adipose tissue (scWAT), in obesity, undergoes trans-differentiation of beige adipocytes to white and, consequently, a hyperplastic growth at later stages. We performed ChIP-seq to profile RNA pol II recruitment and the global epigenetic changes of H3K4me1 and H3K27Ac induced by HFD feeding.
Project description:Adipose tissue shows significant changes during aging. Here, we used single-nucleus RNA-seq to map the single-nucleus transcription profiles of mouse subcutaneous adipose tissue ( SAT ) and visceral adipose tissue ( VAT ) at a single-nucleus resolution, showing the differences in visceral and subcutaneous adipose tissue changes with aging. The mononuclear sequencing method enabled us to restore all major cell types in mouse white adipose tissue, and we characterized adipocytes, immune cells, and preadipocytes. We demonstrated the existence of different adipocyte subsets and showed that aging leads to a decrease in adipogenic subsets. In addition, with aging, both subcutaneous adipose tissue and visceral adipose tissue showed a decrease in immune mechanisms.
Project description:Adipose tissue shows significant changes during aging. Here, we used single-nucleus RNA-seq to map the single-nucleus transcription profiles of mouse subcutaneous adipose tissue ( SAT ) and visceral adipose tissue ( VAT ) at a single-nucleus resolution, showing the differences in visceral and subcutaneous adipose tissue changes with aging. The mononuclear sequencing method enabled us to restore all major cell types in mouse white adipose tissue, and we characterized adipocytes, immune cells, and preadipocytes. We demonstrated the existence of different adipocyte subsets and showed that aging leads to a decrease in adipogenic subsets. In addition, with aging, both subcutaneous adipose tissue and visceral adipose tissue showed a decrease in immune mechanisms.