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Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis

ABSTRACT: Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis

PROVIDER: PRJNA1063722 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27500604_1.fastq.gz	Fastqsanger.gz
	SRR27500604_2.fastq.gz	Fastqsanger.gz
	SRR27500605_1.fastq.gz	Fastqsanger.gz
	SRR27500605_2.fastq.gz	Fastqsanger.gz
	SRR27500606_1.fastq.gz	Fastqsanger.gz

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Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis

Project description:Adaptation to acidosis has been reported to induce a shift towards fatty acid metabolism. We observed that conditioned medium of HCT, FaDu and SiHa adapted to acidosis (pH6.5) induced higher lipolysis of primary subcutaneous and mesenteric adipocytes compared to cancer cells maintained at pH7.4. In order to identify the prolipolytic factors induced by acidosis, we examined the differences between cancer cells adapted to pH6.5 and those maintained at pH7.4 by RNA sequencing. Cancer cells adapted to pH6.5 showed profound alterations in their gene expression compared with cancer cells maintained at pH7.4. Here, we focused on predicted secreted genes. We determined that 84 altered genes predicted to be secreted proteins overlapped between the 3 cancer cell lines, 24 of which were overexpressed. The role of these overexpressed genes was determined in vitro. We studied their role in inducing adipocyte lipolysis and in the depletion of adipose tissue observed in cancer cachexia.

2024-04-05 | GSE253054 | GEO

Transcriptional regulation of adipocyte lipolysis by IRF2BP2 [RNA-seq]

Project description:Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis. Here, we identify the transcriptional factor interferon regulatory factor-2 binding protein 2 (IRF2BP2) as a repressor of adipocyte lipolysis. Deletion of IRF2BP2 in primary human adipocytes increases lipolysis without affecting glucose uptake, whereas IRF2BP2 overexpression decreases lipolysis. RNA-seq and ChIP-seq analyses reveal that IRF2BP2 directly represses several lipolysis-related genes, including LIPE (HSL, hormone sensitive lipase), which encodes the rate-limiting enzyme in lipolysis. Adipocyte-selective deletion of Irf2bp2 in mice increases Lipe expression and free fatty acid levels, resulting in elevated adipose tissue inflammation and glucose intolerance. Altogether, these findings demonstrate that IRF2BP2 restrains adipocyte lipolysis and opens new avenues to target lipolysis for the treatment of metabolic disease.

2024-11-14 | GSE281493 | GEO

Transcriptional regulation of adipocyte lipolysis by IRF2BP2 [ChIP-seq]

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The role of adipocyte lipolysis during dermal fibrosis

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Project description:Transcriptional regulation of adipocyte lipolysis by IRF2BP2 [CUT&RUN]

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Project description:Transcriptional regulation of adipocyte lipolysis by IRF2BP2 [ChIP-seq]

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Lipolysis regulates major transcriptional programs in brown adipocytes

Project description:β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. Here we have used pharmacological inhibitors and a novel direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in brown adipocytes. We show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on brown adipocyte transcription and function.

2022-05-15 | GSE202833 | GEO

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