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Transcriptional analysis of PPARgamma activation in control and PPARgamma null macrophages [GRO-seq]

ABSTRACT: Transcriptional analysis of PPARgamma activation in control and PPARgamma null macrophages [GRO-seq]

PROVIDER: PRJNA436058 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6782092.fastq.gz	Fastqsanger.gz
	SRR6782093.fastq.gz	Fastqsanger.gz
	SRR6782094.fastq.gz	Fastqsanger.gz
	SRR6782095.fastq.gz	Fastqsanger.gz
	SRR6782096.fastq.gz	Fastqsanger.gz

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Transcriptional analysis of PPARgamma activation in control and PPARgamma null macrophages [GRO-seq]

Project description:The nuclear receptor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that macrophage respiration is enhanced by rosiglitazone, an activating PPARgamma ligand, in a PPARgamma dependent manner. Moreover, PPARgamma is required for macrophage respiration even in the absence of exogenous ligand. Unexpectedly, the absence of PPARgamma dramatically affects the oxidation of glutamine. Both glutamine and PPARgamma have been implicated in alternative activation (AA) of macrophages and PPARgamma was required for IL4-dependent gene expression and stimulation of macrophage respiration. Remarkably, depletion of PPARgamma phenocopied the effects of glutamine depletion on transcription. Thus, PPARgamma supports alternative activation by facilitating glutamine metabolism. Yet PPARgamma expression is itself markedly increased by IL4. Thus, PPARgamma functions at the center of a feed forward loop that is central to AA of macrophages.

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Project description:PPARgamma null (PpargΔ/Δ) mice and AZIP mice present a generalized lipodystrophy, accompanied by strong hyperlipidemia and hyperglycemia. Both mouse model develop progressive nephropathy. To shed ligh on the molecular mechanisms underlying the early kidney damage induced by lipodystrophy, we used microarrays to detail the global program of gene expression in whole kidney of PpargΔ/Δ mice and AZIP mice with their respective control mice at 3 weeks of age.

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Transcriptional analysis of PPARgamma activation in control and PPARgamma null macrophages

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