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SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

ABSTRACT: SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

PROVIDER: PRJNA742040 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14931155.fastq.gz	Fastqsanger.gz
	SRR14931156.fastq.gz	Fastqsanger.gz
	SRR14931157.fastq.gz	Fastqsanger.gz
	SRR14931158.fastq.gz	Fastqsanger.gz
	SRR14931159.fastq.gz	Fastqsanger.gz

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SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation

Project description:Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the role of metabolism in the regulation of macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical Th2 cytokine interleukin 4 (IL-4) to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising ROS levels. ROS serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.

2021-07-30 | GSE179066 | GEO

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation.

Project description:Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune-tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the metabolic regulation of macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical T helper 2 cell cytokine interleukin-4 to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising reactive oxygen species levels. Reactive oxygen species serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.

| S-EPMC7611716 | biostudies-literature

Dynamics of SREBP1 binding to DNA in mouse liver

Project description:To systematically understand how the circadian clock and the nutrient-driven rhythm integrate to regulate SREBP1 activity, we evaluated genome-wide the binding of SREBP1 to its targets along the day in wild-type (WT) C57BL/6mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding. In particular, a different phase of expression was observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. The proper temporal expression pattern of these genes was dramatically changed in Bmal1KO mice upon time-restricted feeding, in spite of the rhythmic, although slightly delayed, binding of SREBP1. Our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity exists and is strongly dependent from the circadian core clock. This system allows to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved. 6 samples examined, 6 SREBP1 samples, as well as 6 Polr2b and 6 input samples from GEO series GSE35788 CycliX Consortium was a contributor to this submission.

2014-03-10 | E-GEOD-48375 | biostudies-arrayexpress

Dynamics of SREBP1 binding to DNA in mouse liver

2014-03-10 | GSE48375 | GEO

Caspase-4 mediates SREBP1 activation in macrophages

Project description:We identified caspase-4/S1P/SREBP1 pathway that is activated in LPS-treated macrophages. To analyze the functions of caspase-4 and SREBP1 in gene expression in macrophages, we analyzed the effects of deletions of Casp4 and Srebf1 in bone marrow-derived macrophages by RNA-seq.

2023-01-09 | GSE208374 | GEO

Gene regulated by Srebp1 and c-Myc during reprogramming

Project description:To identify genes regulated by Srebp1 and c-Myc during reprogramming, we performed genome-wide transcriptome profiling in mouse embryonic fibroblasts infected with SKO, SKOM or SKOM plus Srebp1.

2014-11-29 | GSE63705 | GEO

CircPRKAA1 activates a Ku80/Ku70/SREBP1 axis driving de novo fatty acid synthesis in cancer cells

Project description:CircPRKAA1 activates a Ku80/Ku70/SREBP1 axis driving de novo fatty acid synthesis in cancer cells

| PRJNA833292 | ENA

Differences of gene expression profiling of breast cancer cells with stable SREBP1 knockdown and the control cells [MCF-7]

Project description:SREBP1 is a master regulator of lipogenic gene expression. However, the underlying mechanisms of SREBP1-mediated metastasis has not been thoroughly elucidated.We involved microarray to analyze the differences of gene expression profiling between breast cancer cells with stable SREBP1 knockdown and the control cells.

2017-10-21 | GSE105405 | GEO

Differences of gene expression profiling of breast cancer cells with stable SREBP1 knockdown and the control cells [MDA-MB-231]

2017-10-24 | GSE105791 | GEO

Caspase-4 mediates SREBP1 activation in macrophages

Project description:Caspase-4 mediates SREBP1 activation in macrophages

| PRJNA859704 | ENA