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Human Genomics Dec 2019Transcription factors (TFs) consisting of zinc fingers combined with BTB (for broad-complex, tram-track, and bric-a-brac) domain (ZBTB) are a highly conserved protein... (Review)
Review
Transcription factors (TFs) consisting of zinc fingers combined with BTB (for broad-complex, tram-track, and bric-a-brac) domain (ZBTB) are a highly conserved protein family that comprises a multifunctional and heterogeneous group of TFs, mainly modulating cell developmental events and cell fate. LRF/ZBTB7A, in particular, is reported to be implicated in a wide variety of physiological and cancer-related cell events. These physiological processes include regulation of erythrocyte maturation, B/T cell differentiation, adipogenesis, and thymic insulin expression affecting consequently insulin self-tolerance. In cancer, LRF/ZBTB7A has been reported to act either as oncogenic or as oncosuppressive factor by affecting specific cell processes (proliferation, apoptosis, invasion, migration, metastasis, etc) in opposed ways, depending on cancer type and molecular interactions. The molecular mechanisms via which LRF/ZBTB7A is known to exert either physiological or cancer-related cellular effects include chromatin organization and remodeling, regulation of the Notch signaling axis, cellular response to DNA damage stimulus, epigenetic-dependent regulation of transcription, regulation of the expression and activity of NF-κB and p53, and regulation of aerobic glycolysis and oxidative phosphorylation (Warburg effect). It is a pleiotropic TF, and thus, alterations to its expression status become detrimental for cell survival. This review summarizes its implication in different cellular activities and the commonly invoked molecular mechanisms triggered by LRF/ZBTB7A's orchestrated action.
Topics: Adipogenesis; Animals; Erythroid Cells; Humans; Neoplasms; Oncogenes; Transcription Factors; Tumor Suppressor Proteins
PubMed: 31823818
DOI: 10.1186/s40246-019-0252-0 -
Adipocyte Dec 2023Alterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human...
Alterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%. Adipogenesis and lipid and oxidative metabolic gene pathways were enriched in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways were enriched in 3% hydrogels. These data demonstrate that the intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. These observations contribute to a growing literature describing the role of matrix density in regulating adipose tissue function.
Topics: Humans; Adipocytes; Adipose Tissue; Adipogenesis; Hydrogels; Phenotype; Lipids
PubMed: 37815174
DOI: 10.1080/21623945.2023.2268261 -
Biomedicine & Pharmacotherapy =... Nov 2022White adipose tissue expands rapidly due to increased adipocyte number (hyperplasia) and size (hypertrophy), which results in obesity. Adipogenesis is a process of the... (Review)
Review
White adipose tissue expands rapidly due to increased adipocyte number (hyperplasia) and size (hypertrophy), which results in obesity. Adipogenesis is a process of the formation of mature adipocytes from precursor cells. Additionally, obesity-related metabolic complications, such as fatty liver and insulin resistance, are linked to adipogenesis. On the contrary, autophagy is a catabolic process; essential to maintain cellular homeostasis via the degradation or recycling of unnecessary or damaged components. Importantly, autophagy dictates obesity and adipogenesis. Hence, a clear understanding of how autophagy regulates adipogenesis is crucial for drug development and the prevention and treatment of obesity and its associated disorders, such as type 2 diabetes, cardiovascular disease, and cancer. In this review, we highlighted recent findings regarding the crosstalk between adipogenesis and autophagy, as well as the molecules involved. Furthermore, the review discussed how bioactive compounds regulate adipogenesis by manipulating autophagy and underlying molecular mechanisms. Based on in vitro and animal studies, we summarized the effects of bioactive compounds on adipogenesis and autophagy. Hence, human studies are necessary to validate the effectiveness and optimal dosage of these bioactive compounds.
Topics: Animals; Humans; Adipogenesis; Diabetes Mellitus, Type 2; Adipocytes; Autophagy; Obesity
PubMed: 36152415
DOI: 10.1016/j.biopha.2022.113715 -
Adipocyte Dec 2021Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive...
Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear, and many potential therapeutic targets have yet to be discovered. Transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenic differentiation and the potential mechanism in OP9 cells and adipose-derived stem cells. In this study, we found that NADH:ubiquinone oxidoreductase subunit A6 () participates in the regulation of adipogenic differentiation. Furthermore, we show that the effect of Ndufa6 is mediated through stearoyl-CoA desaturase 1 () and demonstrate the inhibitory effect of a SCD1 inhibitor on adipogenesis. Our study broadens the understanding of adipogenic differentiation and offers NDUFA6-SCD1 as a potential therapeutic target for the treatment of obesity.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Cell Differentiation; Stearoyl-CoA Desaturase
PubMed: 34793269
DOI: 10.1080/21623945.2021.2007590 -
International Journal of Biological... 2023Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and... (Review)
Review
Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and brown adipocytes (BAT), which generate heat by burning stored fat (thermogenesis). Emerging evidence indicates that dysregulated adipocyte senescence may disrupt metabolic homeostasis, leading to various diseases and aging. Adipocytes undergo senescence via irreversible cell-cycle arrest in response to DNA damage, oxidative stress, telomere dysfunction, or adipocyte over-expansion upon chronic lipid accumulation. The amount of detectable BAT decreases with age. Activation of cell cycle regulators and dysregulation of adipogenesis-regulating factors may constitute a molecular mechanism that accelerates adipocyte senescence. To better understand the regulation of adipocyte senescence, the effects of post-translational modifications (PTMs), is essential for clarifying the activity and stability of these proteins. PTMs are covalent enzymatic protein modifications introduced following protein biosynthesis, such as phosphorylation, acetylation, ubiquitination, or glycosylation. Determining the contribution of PTMs to adipocyte senescence may identify new therapeutic targets for the regulation of adipocyte senescence. In this review, we discuss a conceptual case in which PTMs regulate adipocyte senescence and explain the mechanisms underlying protein regulation, which may lead to the development of effective strategies to combat metabolic diseases.
Topics: Adipose Tissue, Brown; Adipocytes, Brown; Adipogenesis; Protein Processing, Post-Translational; Cell Cycle Checkpoints
PubMed: 37928271
DOI: 10.7150/ijbs.86404 -
Scientific Data Jun 2023Adipogenesis is a process in which fat-specific progenitor cells (preadipocytes) differentiate into adipocytes that carry out the key metabolic functions of the adipose...
Adipogenesis is a process in which fat-specific progenitor cells (preadipocytes) differentiate into adipocytes that carry out the key metabolic functions of the adipose tissue, including glucose uptake, energy storage, and adipokine secretion. Several cell lines are routinely used to study the molecular regulation of adipogenesis, in particular the immortalized mouse 3T3-L1 line and the primary human Simpson-Golabi-Behmel syndrome (SGBS) line. However, the cell-to-cell variability of transcriptional changes prior to and during adipogenesis in these models is not well understood. Here, we present a single-cell RNA-Sequencing (scRNA-Seq) dataset collected before and during adipogenic differentiation of 3T3-L1 and SGBS cells. To minimize the effects of experimental variation, we mixed 3T3-L1 and SGBS cells and used computational analysis to demultiplex transcriptomes of mouse and human cells. In both models, adipogenesis results in the appearance of three cell clusters, corresponding to preadipocytes, early and mature adipocytes. These data provide a groundwork for comparative studies on these widely used in vitro models of human and mouse adipogenesis, and on cell-to-cell variability during this process.
Topics: Humans; Adipocytes; Adipogenesis; Adipose Tissue; Cell Differentiation; Transcriptome; Animals; Mice; Single-Cell Gene Expression Analysis
PubMed: 37328521
DOI: 10.1038/s41597-023-02293-x -
Current Opinion in Clinical Nutrition... Nov 2018The current review provides an update on secreted factors and mechanisms that promote a thermogenic program in beige adipocytes, and their potential roles as therapeutic... (Review)
Review
PURPOSE OF REVIEW
The current review provides an update on secreted factors and mechanisms that promote a thermogenic program in beige adipocytes, and their potential roles as therapeutic targets to fight obesity.
RECENT FINDINGS
We outline recent studies revealing unrecognized mechanisms controlling beige adipocyte physiology, and summarize in particular those that underlie beige thermogenesis independently of classical uncoupling. We also update strategies aimed at fostering beige adipogenesis and white-to beige adipocyte conversion. Finally, we summarize newly identified endogenous secreted factors that promote the thermogenic activation of beige adipocytes and discuss their therapeutic potential.
SUMMARY
The identification of novel endogenous factors that promote beiging and regulate beige adipocyte-specific physiological pathways opens up new avenues for therapeutic engineering targeting obesity and related metabolic disorders.
Topics: Adipocytes, Beige; Adipocytes, White; Adipogenesis; Animals; Humans; Obesity; Thermogenesis
PubMed: 30148740
DOI: 10.1097/MCO.0000000000000509 -
Molecules and Cells May 2023Obesity is a significant global health risk that can cause a range of serious metabolic problems, such as type 2 diabetes and cardiovascular diseases. Adipose tissue... (Review)
Review
Obesity is a significant global health risk that can cause a range of serious metabolic problems, such as type 2 diabetes and cardiovascular diseases. Adipose tissue plays a pivotal role in regulating energy and lipid storage. New research has underlined the crucial role of splicing factors in the physiological and functional regulation of adipose tissue. By generating multiple transcripts from a single gene, alternative splicing allows for a greater diversity of the proteome and transcriptome, which subsequently influence adipocyte development and metabolism. In this review, we provide an outlook on the part of splicing factors in adipogenesis and thermogenesis, and investigate how the different spliced isoforms can affect the development and function of adipose tissue.
Topics: Humans; Adipogenesis; Diabetes Mellitus, Type 2; RNA Splicing Factors; Adipose Tissue; Thermogenesis
PubMed: 37170770
DOI: 10.14348/molcells.2023.2195 -
Genes Jan 2024Pericytes (PCs) are located surrounding the walls of small blood vessels, particularly capillaries and microvessels. In addition to their functions in maintaining... (Review)
Review
Pericytes (PCs) are located surrounding the walls of small blood vessels, particularly capillaries and microvessels. In addition to their functions in maintaining vascular integrity, participating in angiogenesis, and regulating blood flow, PCs also serve as a reservoir for multi-potent stem/progenitor cells in white, brown, beige, and bone marrow adipose tissues. Due to the complex nature of this cell population, the identification and characterization of PCs has been challenging. A comprehensive understanding of the heterogeneity of PCs may enhance their potential as therapeutic targets for metabolic syndromes or bone-related diseases. This mini-review summarizes multiple PC markers commonly employed in lineage-tracing studies, with an emphasis on their contribution to adipogenesis and functions in different adipose depots under diverse metabolic conditions.
Topics: Adipogenesis; Pericytes; Adipose Tissue; Stem Cells; Capillaries
PubMed: 38275607
DOI: 10.3390/genes15010126 -
Biochemical and Biophysical Research... Apr 2023Obesity is commonly associated with excessive adipogenesis, a process by which preadipocytes undergo differentiation into mature adipocytes; however, the mechanisms...
Obesity is commonly associated with excessive adipogenesis, a process by which preadipocytes undergo differentiation into mature adipocytes; however, the mechanisms underlying adipogenesis are not completely understood. Potassium channel tetramerization domain-containing 17 (Kctd17) belongs to the Kctd superfamily and act as a substrate adaptor of the Cullin 3-RING E3 ubiquitin ligase, which is involved in a wide variety of cell functions. However, its function in the adipose tissue remains largely unknown. Here, we found that Kctd17 expression levels were increased in white adipose tissue, especially in adipocytes, in obese mice compared to lean control mice. Gain or loss of function of Kctd17 in preadipocytes inhibited or promoted adipogenesis, respectively. Furthermore, we found that Kctd17 bound to C/EBP homologous protein (Chop) to target it for ubiquitin-mediated degradation, and this process was likely associated with increased adipogenesis. In conclusion, these data suggest that Kctd17 plays an important role in adipogenesis and can be a novel therapeutic target for obesity.
Topics: Animals; Mice; 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Cell Differentiation; Obesity
PubMed: 36868076
DOI: 10.1016/j.bbrc.2023.02.068