Blocking YY1 in adipocytes decouples thermogenic capacity from metabolic benefits by generating spermidine
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ABSTRACT:
PROVIDER: PRJNA1137870 | ENA |
REPOSITORIES: ENA
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Project description:Traditional ideas hold that the accumulation of mitochondria in thermogenic adipose tissue, namely brown and beige fat, helps to increase energy expenditure (EE), thereby alleviating obesity and metabolic disorders. However, recent studies in mice have shown that knocking out key proteins that maintain mitochondrial function can inhibit the activation of thermogenic fat while somehow protecting the mice from high-fat diet (HFD)–induced metabolic disorders. Therefore, the specific role of adipose mitochondria in metabolic benefits needs further analysis. Here, our use of non-biased sequencing-based screening identified YY1 as a key player in maintaining mitochondrial function in thermogenic adipose tissue. YY1 promotes the transcription of electron transport chain (ETC) genes during thermogenesis; thus, YY1 adipose knockout (YAKO) mice showed reduced body temperature and EE under cold stress. Interestingly, YAKO mice showed alleviation of HFD-induced obesity and insulin resistance, which can be attributed to a repression of adipose tissue inflammation. Metabolomic analysis revealed that blocking YY1 in adipocytes directs glucose metabolism toward lactate, enhances the uptake of glutamine, and promotes the production of anti-inflammatory spermidine. Blocking spermidine production can reverse the beneficial metabolic effects observed in YAKO mice. In summary, our findings reveal a metabolic reprogramming pathway centered on adipose mitochondria; that is, although blocking YY1 reduced the mitochondria content, it generated spermidine and alleviated adipose inflammation, therefore leads to a thermogenic capacity-metabolic benefits uncoupling phenomenon.
2024-08-26 | GSE272637 | GEO
Project description:Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
2012-01-04 | E-MTAB-912 | biostudies-arrayexpress
Project description:To compare the effects of spermidine, key polyamine, on the gene expression profile of organ cultured human hair follicles Vehicle treated Vs. 0.5 µM spermidine treatment. Two control samples, two spermidine treated samples
2011-04-16 | E-GEOD-28650 | biostudies-arrayexpress
Project description:To achieve extreme spermidine stress we used DspeG E. coli strain. We identified the pathways that are altered under spermidine stress. Among many changes spermidine altered the iron-sulfur cluster metabolism and redox balance in the cells. Therefore, we have shown that superoxide quencher, NAC and ascorbate mitigates spermidine stress. Overall our data explains the importaance of tight spermidine homeostasisin the cell.
2021-09-01 | GSE154618 | GEO
Project description:To achieve extreme spermidine stress we used DspeG E. coli strain. We identified the pathways that are altered under spermidine stress. Among many changes spermidine altered the iron-sulfur cluster metabolism and redox balance in the cells. Therefore, we have shown that superoxide quencher, NAC and ascorbate mitigates spermidine stress. Overall our data explains the importaance of tight spermidine homeostasisin the cell.
2022-03-01 | GSE186526 | GEO
Project description:The naturally occurring polyamines putrescine, spermidine or spermine are ubiquitous in all cells. Although polyamines have prominent regulatory roles in cell division and growth, precise molecular and cellular functions are not well established in vivo. In this work we have performed a microarray experiment in a polyamine mutant (delta-spe3 delta-fms1) strain to investigate the responsiveness of yeast genes to supplementation with spermidine and spermine. Expression analysis identified genes responsive to the addition of either excess spermidine (10-5 M) or spermine (10-5 M) compared to a control culture containing 10-8 M spermidine. 247 genes were up-regulated >2-fold, and 11 genes were up-regulated more than 10-fold after spermidine addition. Functional categorization of the genes showed induction of transport related genes, and genes involved in methionine, arginine, lysine, NAD and biotin biosynthesis. 268 genes were down-regulated more than 2-fold, and 6 genes were down-regulated more than 8-fold after spermidine addition. A majority of the down-regulated genes are involved in nucleic acid metabolism and various stress responses. In contrast, only few genes (18) were significantly responsive to spermine. Thus, results from global gene expression profiling demonstrate a more major role for spermidine in modulating gene expression in yeast than spermine. Experiment Overall Design: 5 control replicates vs. 3 spermine (SP)-treated or 5 spermidine (SPD)-treated samples.
2009-09-05 | E-GEOD-15269 | biostudies-arrayexpress
Project description:Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends lifespan, while it exerts cardioprotective effects through reduction of cardiac hypertrophy and preservation of diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy, mitochondrial respiration and mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine failed to promote cardioprotection in mice lacking the autophagy-related gene Atg5 in cardiomyocytes. In Dahl salt-sensitive rats fed high-salt diet, a model for hypertension-induced congestive heart failure, spermidine reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. Finally, high dietary spermidine intake correlated with reduced blood pressure and a lower incidence of cardiovascular disease in humans. Our results suggest a novel and generic strategy against cardiovascular disease.
2016-11-13 | GSE86882 | GEO
Project description:Recently, we have elucidated a novel role for the oncometabolite spermidine; intracellular spermidine is well-characterized as an essential metabolic fuel in growing cancer cells, but extracellular spermidine, released by dying cancer cells, also contributes to tumor progression by impairing effector activities of CD8+ T cells through the interference with proximal TCR signal transduction. In order to decipher how spermidine modulates T cell signaling and effector programs, we conducted a comprehensive gene expression analysis by microarray for in vitro cultured mouse CD8+ T cells treated with or without spermidine.
2023-04-01 | GSE216472 | GEO
Project description:mRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
2013-09-01 | E-GEOD-38998 | biostudies-arrayexpress
Project description:To compare the effects of spermidine, key polyamine, on the gene expression profile of organ cultured human hair follicles
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