Coordinated metabolic transitions and gene expression by NAD+ during adipogenesis.
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ABSTRACT:
PROVIDER: PRJNA739727 | ENA |
REPOSITORIES: ENA
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Project description:Adipocytes are the main cell type in adipose tissue, a critical regulator of metabolism, highly specialized in storing energy as fat. Adipocytes differentiate from multipotent mesenchymal stromal cells through adipogenesis. Using RNA-seq we explored the effect of manipulating NAD+ bioavailability during adipogenic differentiation from human mesenchymal stem cells. Cells were harvested either undifferentiated (hMSC) or after days 8 and 16 of adipogenic induction. During adipogenesis, cells were treated with either NAD+ (5 mM), or FK866 (1 nM) or EX527 (50 μM).
2022-09-16 | GSE178615 | GEO
Project description:Adipocytes are the main cell type in adipose tissue, which is a critical regulator of metabolism, highly specialized in storing energy as fat. Adipocytes differentiate from multipotent mesenchymal stromal cells (hMSCs) through adipogenesis, a tightly controlled differentiation process involving close interplay between metabolic transitions and sequential programs of gene expression. However, the specific gears driving this interplay remain largely obscure. Additionally, the metabolite nicotinamide adenine dinucleotide (NAD+) is becoming increasingly recognized as a regulator of lipid metabolism, and a promising therapeutic target for dyslipidemia and obesity. Here, we explored how NAD+ bioavailability controls adipogenic differentiation from hMSC. We found a previously unappreciated repressive role for NAD+ on adipocyte commitment, while a functional NAD+-dependent deacetylase SIRT1 appeared crucial for terminal differentiation of pre-adipocytes. Repressing NAD+ biosynthesis during adipogenesis promoted the adipogenic transcriptional program, while two-photon microscopy and extracellular flux analyses suggest that SIRT1 activity mostly relies on the metabolic switch. Interestingly, SIRT1 controls subcellular compartmentalization of redox metabolism during adipogenesis.
| S-EPMC9538974 | biostudies-literature
Project description:White adipocytes function as the major energy reservoir in humans by storing large amounts of triglycerides. Their dysfunction is associated with metabolic disorders. However, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generated a spatiotemporal proteomic atlas of human adipogenesis to gain insights into cellular remodeling and the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation. Our study highlights the coordinated regulation of protein localization and abundance during adipogenesis. More specifically, we identified a compartment-specific regulation of protein levels to reprogram branched chain amino acid and one-carbon metabolism to provide building blocks and reduction equivalents for lipid synthesis. Additionally, we identified C19orf12 as a differentiation induced adipocyte-specific lipid droplet (LD) protein, which interacts with the translocase of the outer membrane (TOM) complex of LD associated mitochondria and modulates adipocyte lipid storage. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.
2024-01-17 | PXD047412 | Pride
Project description:Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme regulating cellular energy metabolism across all species. Recent studies have shown the pleiotropic roles of adipose tissue NAD+ biology in adipose tissue and whole-body metabolism. The major purpose of the present study was to test the hypothesis that adipose tissue NAD+ biosynthesis, mediated by nicotinamide phosphoribosyltransferase (NAMPT), is a physiological regulator of whole-body metabolic flexibility. To this end, we analyzed adipocyte-specific Nampt knockout (ANKO) mice and subcutaneous white adipose tissue (WAT) biopsy samples obtained from human subjects. We found ANKO mice preferably utilized glucose substrate during the light period or after prolonged fasting. In contrast, ANKO mice had marked decreases in stimulation of glucose oxidation and suppression of fat oxidation during the postprandial status despite hyperinsulinemia. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT causes inflammation, oxidative stress, defective fatty acid oxidation, and mitochondrial dysfunction in WAT, key features of obesity and metabolic inflexibility. We also found WAT NAD+ concentration was decreased in people with obesity and insulin resistance compared with those who were non-obese and insulin-sensitive. In addition, bariatric surgery-induced 20% weight loss increased WAT NAD+ concentration in people with obesity. Taken together, our results reveal the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility. Our results also provide translational and clinical insight into adipose tissue NAD+ biology in obesity and whole-body metabolic health.
2021-07-01 | GSE159397 | GEO
Project description:Metabolic Transitions Define the Spermatogonial Stem Cell Maturation
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Project description:How hematopoietic stem cells (HSCs) maintain metabolic homeostasis to support tissue repair and regeneration throughout the lifespan is elusive. Here we show that CD38, a NAD+ metabolic enzyme, promotes HSC proliferation by inducing mitochondrial Ca2+ influx and mitochondrial metabolism at young age. Conversely, aberrant CD38 upregulation during aging is a driver of HSC deterioration due to compromised mitochondrial stress management. Pharmacological inactivation of CD38 reverses HSC aging and the pathophysiological changes of the aging hematopoietic system. Blocking mitochondrial Ca2+ influx inhibits HSC proliferation at young age yet prevents HSC aging. Our study highlights a NAD+ metabolic checkpoint that balances mitochondrial activation to support HSC proliferation and mitochondrial stress to enhance HSC self-renewal throughout the lifespan, and links aberrant Ca2+ signaling to HSC aging.
2024-05-28 | GSE268310 | GEO
Project description:Extracellular signaling and nutrient availability are major factors for cell fate decision. Responds to extracellular information requires metabolic alterations and differential gene expression. However, how cells integrate extracellular signals (e.g. hormones) and cellular metabolic status to coordinate transcriptional outcome is poorly understood. We hypothesized that fluctuations in nuclear nicotinamide adenine dinucleotide (NAD+) levels act as a signal to integrate cellular glucose metabolism and transcription program during adipocyte differentiation. To test this hypothesis, we performed RNA-seq on control, Nmnat1 and Parp1 knockdown 3T3-L1 cells during various time point of differentiation.
2018-03-17 | GSE96764 | GEO
Project description:Metabolic Transitions Define the Spermatogonial Stem Cell Maturation [mouse]
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Project description:Metabolic Transitions Define the Spermatogonial Stem Cell Maturation [human]
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