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Curated gene expression dataset of differentiating 3T3-L1 adipocytes under pharmacological and genetic perturbations.

ABSTRACT: The 3T3-L1 cell line is used as an adipocyte differentiation model for the analysis of genes specifically expressed during the differentiation course. This cell model has several applications in obesity and insulin resistance research. We built a data resource to model gene expression of differentiating and mature adipocytes in response to several drugs and gene manipulations. We surveyed the literature survey for microarray datasets of differentiating 3T3-L1 cell line sampled at one or more time points under genetic or pharmacological perturbations. Data and metadata were obtained from the gene expression omnibus. The metadata were manually curated using unified language across the studies. Probe intensities were mapped and collapsed to genes using a reproducible pipeline. Samples were classified into none, genetically or pharmacologically modified. In addition to the clean datasets, two aggregated sets were further homogenized for illustration purposes. The curated datasets are available as an R/Bioconductor experimental data package curatedAdipoArray. The package documents the source code of the data collection, curation and processing. Finally, we used a subset of the data to effectively remove batch effects and reproduce biological observations. Database URL https://bioconductor.org/packages/curatedAdipoArray.

SUBMITTER: Ahmed M

PROVIDER: S-EPMC7553567 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion. Short-chain peptides were among several small molecules that were increased during mitotic clonal expansion. Additional indicators of protein turnover were also increased, including bilirubin, a degradation product of heme-containing proteins, and 3-methylhistidine, a post-translationally modified amino acid that is not reutilized for protein synthesis. To study the origin of the peptides, we treated differentiating preadipocytes with 18O labeled water and found that 18O was incorporated into the short chain peptides, confirming them, at least in part, as products of hydrolysis. Inhibitors of the proteasome or matrix metalloproteinases affected the peptide levels during differentiation, but inhibitors of autophagy or peptidases did not. 18O was also incorporated into several choline metabolites including cytidine 5'-diphosphocholine (CDP-choline), glycerophosphocholine, and several phosphatidylcholine species, indicative of phosphatidylcholine synthesis/degradation and of flux through the CDP-choline cycle, a hallmark of proliferating cells. 18O-Tracer metabolomics further showed metabolic labeling of glutamate, suggestive of glutaminolysis, also characteristic of proliferating cells. Together, these results highlight the utility of 18O isotope labeling in combination with metabolomics to uncover changes in cellular metabolism that are not detectable by time-resolved metabolomics.

Dataset Information

Curated gene expression dataset of differentiating 3T3-L1 adipocytes under pharmacological and genetic perturbations.

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