Data on changes in lipid profiles during differentiation and maturation of human subcutaneous white adipocytes analyzed using chromatographic and bioinformatics tools
Project description:In this dataset, we have described the changes in the lipid profile occurring during the differentiation and maturation of cultured human subcutaneous white preadipocytes into mature adipocytes. We divided three cell lines of Caucasian-derived subcutaneous preadipocytes into five stages (stage-1 to stage-5), from subcutaneous preadipocytes to mature subcutaneous adipocytes filled with many lipid droplets. Lipids were extracted from the cells at each stage by employing the Bligh and Dyer method and processed using untargeted liquid chromatography coupled with Q-Exactive Orbitrap tandem mass spectrometry. The lipids were identified using LipidSearch 4.2.13, and statistical analysis was performed using MetaboAnalyst 5.0. Dendrogram and principal component analysis clearly separated different stages of cells such as subcutaneous preadipocytes (stage-1), after the induction of differentiation into adipocytes (stage-2), and after the start of fat accumulation (stage-3 to stage-5). Of the 309 lipid species detected in LipidSearch 4.2.13, a total of 145 were statistically significant (false discovery rate < 0.05). The data are available at Metabolomics Workbench, Study ID ST001958: [https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Project&ProjectID=PR001245].
Project description:Previously, we reported changes in the lipid profile of cultured human subcutaneous white preadipocytes during their differentiation and maturation. Here, using the same cells, we report changes in the protein profiles during differentiation and maturation as multi-omics data. The three cell lines of Caucasian-derived subcutaneous preadipocytes were divided into five stages: stage-1, subcutaneous preadipocytes; stage-2, following induction of differentiation into adipocytes; stages-3 to -5, from the initiation of lipid droplet formation to mature subcutaneous adipocytes (depending on the lipid droplet amount and formation). In each stage, proteins were extracted from the cells, proteolytically cleaved, and analyzed using untargeted liquid chromatography and mass spectrometry. The proteins were then identified and statistically analyzed. A total of 1,871 proteins were identified with high confidence, of which, 381 were statistically significant (P-value < 0.05) between any two stages. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the proteins significantly altered during the differentiation and maturation of preadipocytes were enriched in various pathways, including "ribosome," "Coronavirus disease-COVID-19," and "extracellular matrix (ECM)-receptor interaction" (FDR < 0.05).
Project description:We analyzed changes in the protein profiles that occur during differentiation and maturation of cultured human subcutaneous white preadipocytes. We divided the three cell lines (Cell Line-1, Cell Line-2, and Cell Line-3) of Caucasian-derived subcutaneous preadipocytes into five stages: i) subcutaneous preadipocytes as stage-1, ii) after inducing differentiation into adipocytes as stage-2, iii-v) from the initiation of lipid droplet formation to become mature subcutaneous adipocytes was defined as stage-3 to stage-5, depending on lipid droplet amount and formation. Proteins from the cells were extracted at each stage (stage-1 to stage-5), proteolytically cleaved using trypsin, and analyzed using untargeted liquid chromatography and mass spectrometry.
Project description:BackgroundPekin duck is an important animal model for its ability for fat synthesis and deposition. However, transcriptional dynamic regulation of adipose differentiation driven by complex signal cascades remains largely unexplored in this model. This study aimed to explore adipogenic transcriptional dynamics before (proliferation) and after (differentiation) initial preadipocyte differentiation in ducks.ResultsExogenous oleic acid alone successfully induced duck subcutaneous preadipocyte differentiation. We explored 36 mRNA-seq libraries in order to study transcriptome dynamics during proliferation and differentiation processes at 6 time points. Using robust statistical analysis, we identified 845, 652, 359, 2401 and 1933 genes differentially expressed between -48 h and 0 h, 0 h and 12 h, 12 h and 24 h, 24 h and 48 h, 48 h and 72 h, respectively (FDR < 0.05, FC > 1.5). At the proliferation stage, proliferation related pathways and basic cellular and metabolic processes were inhibited, while regulatory factors that initiate differentiation enter the ready-to-activate state, which provides a precondition for initiating adipose differentiation. According to weighted gene co-expression network analysis, pathways positively related to adipogenic differentiation are significantly activated at the differentiation stage, while WNT, FOXO and other pathways that inhibit preadipocyte differentiation are negatively regulated. Moreover, we identified and classified more than 100 transcription factors that showed significant changes during differentiation, and found novel transcription factors that were not reported to be related to preadipoctye differentiation. Finally, we manually assembled a proposed regulation network model of subcutaneous preadipocyte differentiation base on the expression data, and suggested that E2F1 may serve as an important link between the processes of duck subcutaneous preadipocyte proliferation and differentiation.ConclusionsFor the first time we comprehensively analyzed the transcriptome dynamics of duck subcutaneous preadipocyte proliferation and differentiation. The current study provides a solid basis for understanding the synthesis and deposition of subcutaneous fat in ducks. Furthermore, the information generated will allow future investigations of specific genes involved in particular stages of duck adipogenesis.
Project description:Beiging of white adipose tissue (WAT) has beneficial effects on metabolism. Although it is known that beige adipocytes are active in lipid catabolism and thermogenesis, how they are regulated deserves more explorations. In this study, we demonstrate that stearoyl-CoA desaturase 1 (SCD1) in subcutaneous WAT (scWAT) responded to cold stimulation and was able to promote mobilization of triacylglycerol [TAG (triglyceride)]. In vitro studies showed that SCD1 promoted lipolysis in C3H10T1/2 white adipocytes. The lipolytic effect was contributed by one of SCD1's products, oleic acid (OA). OA upregulated adipose TAG lipase and hormone-sensitive lipase expression. When SCD1 was overexpressed in the scWAT of mice, lipolysis was enhanced, and oxygen consumption and heat generation were increased. These effects were also demonstrated by the SCD1 knockdown experiments in mice. In conclusion, our study suggests that SCD1, known as an enzyme for lipid synthesis, plays a role in upregulating lipid mobilization through its desaturation product, OA.
Project description:Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7-63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test-retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI.
Project description:Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFβ ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.
Project description:Emerging evidence in the field of adolescent neurodevelopment suggests that pubertal processes may contribute to known trajectories of brain maturation, and may contribute, in part, to sex differences in related cognitive, behavioral and mental health outcomes. The current longitudinal study examined how changes in physical pubertal maturation (measured by the Peterson Developmental Scale) predict changes in white matter microstructure in 18 boys and 15 girls over an approximate 2-year follow-up period, while accounting for age. Using Tract-Based Spatial Statistics and multi-level modeling, the results showed that physical pubertal changes predict patterns of changes in fractional anisotropy (FA) in white matter regions in the thalamus, precentral gyrus, superior corona radiata, corpus callosum (genu), superior corona radiata, and superior frontal gyrus. Sex specific changes were also seen, as changes in gonadal and adrenal development related to increases in FA in the superior frontal gyrus and precentral gyrus in boys, but gonadal development related to decreases in FA in the anterior corona radiata in girls. These findings are the first to show how changes over time in pubertal development influence white matter development. In addition, they support a larger body of emerging research suggesting that pubertal processes contribute to distinct changes in boys and girls across brain development.
Project description:Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 ± 10.39 kg) were randomly divided into two treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 d. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of the lipolytic gene (hormone-sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially ceramides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorγ (PPARγ) expression and further inhibit adipogenic differentiation in adipose tissues of pigs by suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short-chain fatty acids (SCFAs) in the gut (P ≤ 0.05) but the abundance of Cers was negatively related to the production and functions of SCFAs (P ≤ 0.05). CLAs altered the distribution of the lipid in serum and inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing PPARγ expression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.
Project description:IntroductionApproximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.ObjectivesThe goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy.MethodsFT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5).ResultsDistinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane.ConclusionGenerally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.