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Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins

ABSTRACT: Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins

PROVIDER: PRJNA813623 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18220721.fastq.gz	Fastqsanger.gz
	SRR18220722.fastq.gz	Fastqsanger.gz
	SRR18220723.fastq.gz	Fastqsanger.gz
	SRR18220724.fastq.gz	Fastqsanger.gz
	SRR18220725.fastq.gz	Fastqsanger.gz

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Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [Ribo-seq]

Project description:Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [Ribo-seq]

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Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [RNA-seq]

Project description:Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [RNA-seq]

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Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [RNA-seq]

Project description:The absence of thousands of recently annotated small open reading frame (smORF)-encoded peptides and small proteins (microproteins) from databases has precluded their analysis in metabolism and metabolic disease. Given the outsized importance of small proteins and peptides in metabolism—insulin, leptin, amylin, glucagon, and glucagon-like peptide-1 (GLP-1)—microproteins are a potentially rich source of uncharacterized metabolic regulators. Here, we annotate smORFs in primary differentiated brown, white, and beige mouse adipose cells. Ribosome profiling (Ribo-Seq) detected a total of 3,877 unannotated smORFs. Analysis of RNA-Seq datasets revealed diet-regulated smORF expression in adipose tissues, and validated the adipose translation of the feeding-neuron marker gene Gm8773. Gm8773 encodes the mouse homolog of FAM237B, a neurosecretory protein that stimulates food intake and promotes weight gain in chickens. Testing of recombinant mFAM237B produced similar orexigenic activity in mice further supporting a role for FAM237B a metabolic regulator and part of the brain-adipose axis. Furthermore, we showed that data independent acquisition mass spectrometry (DIA-MS) proteomics can provide a sensitive, flexible, and quantitative platform for identifying microproteins by mass spectrometry. Using this system led to the detection of 58 microproteins from cell culture and an additional 25 from mouse serum. The proteomics data established the anti-inflammatory microprotein AW112010 as a circulating factor, and found that serum levels of a microprotein translated from a FRS2 uORF is elevated in older obese mice. Together, the data highlight the value of this database in examining understudied smORFs and microproteins in metabolic research and identifying additional regulators of metabolism.

2022-12-13 | GSE198107 | GEO

Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins [Ribo-seq]

2022-12-13 | GSE197909 | GEO

Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins.

Project description:Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.

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Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant small ORFs and Functional Microproteins

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-13 | GSE198109 | GEO

White-to-brown metabolic conversion of human adipocytes by JAK inhibition

Project description:The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that permanently confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. Human pluripotent stem-cell derived mesenchymal progenitor cells (PSC-MPCs), white adipose cells (PSC-WA), and brown adipose cells (PSC-BA) were treated with DMSO (as control), a JAK3-inhibitor compound, and a SYK-inhibitor compound respectively. Transcriptomic expression profiling was performed at 24 hours and 7 days respectively. Three biological replicates are available for each condition defined by cell type, compound, and time.

2014-10-31 | E-GEOD-57896 | biostudies-arrayexpress

White-to-brown metabolic conversion of human adipocytes by JAK inhibition

2014-10-31 | GSE57896 | GEO

Expression Data from Bone Marrow Progenitor-Derived Adipocytes, White Adipocytes and Brown Adipocytes.

Project description:We have identified a population of adipocytes in fat tissue that arise from bone marrow-derived progenitor cells. We used microarrays to compare the global gene expression patterns of the bone marrow progenitor-derived adipocytes as well as conventional white and brown adipocytes to evaluate the relationship between these adipocyte subpopulations. Gonadal fat tissue (for white adipocytes) and intrascapular fat tissue (for brown adipocytes) was digested with collagenase and adipocytes were recovered by centrifugation/flotation. Bone marrow derived adipocytes were isolated from the adipocyte fraction of gonadal fat tissue from mice receiving bone marrow tranplants from donors expressing either green fluorescent protein (GFP) or beta-galactosidase (LacZ) by flow cytometry.

2010-01-08 | E-GEOD-19757 | biostudies-arrayexpress

Expression Data from Bone Marrow Progenitor-Derived Adipocytes, White Adipocytes and Brown Adipocytes.

2010-01-08 | GSE19757 | GEO