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Gene Aug 2023Ubiquitination is a widespread post-transcriptional modification (PTM) that occurs during protein degradation in eukaryotes and participates in almost all physiological... (Review)
Review
Ubiquitination is a widespread post-transcriptional modification (PTM) that occurs during protein degradation in eukaryotes and participates in almost all physiological and pathological processes, including animal adipogenesis. Ubiquitination is a cascade reaction regulated by the activating enzyme E1, conjugating enzyme E2, and ligase E3. Several recent studies have reported that E3 ligases play important regulatory roles in adipogenesis. However, as a key influencing factor for the recognition and connection between the substrate and ubiquitin during ubiquitination, its regulatory role in adipogenesis has not received adequate attention. In this review, we summarize the E3s' regulation and modification targets in animal adipogenesis, explain the regulatory mechanisms in lipogenic-related pathways, and further analyze the existing positive results to provide research directions of guiding significance for further studies on the regulatory mechanisms of E3s in animal adipogenesis.
Topics: Animals; Adipogenesis; Ubiquitination; Ubiquitin-Protein Ligases; Ubiquitin; Proteolysis; Ubiquitin-Conjugating Enzymes
PubMed: 37336271
DOI: 10.1016/j.gene.2023.147574 -
Aging Oct 2023Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin...
Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin resistance. However, its underlying mechanism remains unclear. In this study, we show that senescence-associated inflammation and suppressed adipogenesis play a role in subcutaneous adipose tissue reduction and dysfunction in WS. Clinical data from four Japanese patients with WS revealed significant associations between the decrease of areas of subcutaneous fat and increased insulin resistance measured by the glucose clamp. Adipose-derived stem cells from the stromal vascular fraction derived from WS subcutaneous adipose tissues (WSVF) showed early replicative senescence and a significant increase in the expression of senescence-associated secretory phenotype (SASP) markers. Additionally, adipogenesis and insulin signaling were suppressed in WSVF, and the expression of adipogenesis suppressor genes and SASP-related genes was increased. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), alleviated premature cellular senescence, rescued the decrease in insulin signaling, and extended the lifespan of WS model of . To the best of our knowledge, this study is the first to reveal the critical role of cellular senescence in subcutaneous lipoatrophy and severe insulin resistance in WS, highlighting the therapeutic potential of rapamycin for this disease.
Topics: Animals; Humans; Werner Syndrome; Adipogenesis; Insulin Resistance; Caenorhabditis elegans; Cellular Senescence; Subcutaneous Fat; Lipodystrophy; Inflammation; Sirolimus; Insulins; Mammals
PubMed: 37793000
DOI: 10.18632/aging.205078 -
International Journal of Biological... Dec 2023Adipogenesis is a complex biological process. However, the regulatory mechanism of circRNAs in adipogenesis is still unclear. In this study, we identified a novel...
Adipogenesis is a complex biological process. However, the regulatory mechanism of circRNAs in adipogenesis is still unclear. In this study, we identified a novel circRNA, circBTBD7, which was highly expressed in adipose tissue and peaked at two days after differentiation in bovine primary adipocytes. When circBTBD7 was knocked down in bovine primary adipocytes, the lipid droplets accumulation was significantly increased. Furthermore, the expression of adipocyte differentiation markers (PPARγ and C/EBPα) and lipogenic genes (FABP4, FASN and ACCα) were significantly upregulated. Moreover, circBTBD7 was mainly located in the cytoplasm, which indicated it was probably to act as competitive endogenous RNAs (ceRNAs). Subsequently, the dual luciferase reporter assay showed that circBTBD7 could bind to miR-183. Further, miR-183 promoted adipogenesis by inhibiting SMAD4. What's more, the rescue assays showed that circBTBD7 attenuated the inhibition of SMAD4 expression by sponging miR-183. In summary, these results suggested that circBTBD7 inhibited adipogenesis via the miR-183/SMAD4 axis.
Topics: Animals; Cattle; Adipogenesis; MicroRNAs; Adipocytes; Adipose Tissue; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation
PubMed: 37689299
DOI: 10.1016/j.ijbiomac.2023.126740 -
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 =... Oct 2023The association among increased inflammation, disrupted iron homeostasis, and adipose tissue dysfunction in obesity has been widely recognized. However, the specific...
The association among increased inflammation, disrupted iron homeostasis, and adipose tissue dysfunction in obesity has been widely recognized. However, the specific impact of inflammation on iron homeostasis during human adipogenesis and in adipocytes remains poorly understood. In this study, we investigated the effects of bacterial lipopolysaccharide (LPS) on iron homeostasis during human adipocyte differentiation, in fully differentiated adipocytes, and in human adipose tissue. We found that LPS-induced inflammation hindered adipogenesis and led to a gene expression profile indicative of intracellular iron accumulation. This was accompanied by increased expression of iron importers (TFRC and SLC11A2), markers of intracellular iron accumulation (FTH, CYBA, FTL, and LCN2), and decreased expression of iron exporter-related genes (SLC40A1), concomitant with elevated intracellular iron levels. Mechanistically, RNA-seq analysis and gene knockdown experiments revealed the significant involvement of iron importers SLC39A14, SLC39A8, and STEAP4 in LPS-induced intracellular iron accumulation in human adipocytes. Notably, markers of LPS signaling pathway-related inflammation were also associated with a gene expression pattern indicative of intracellular iron accumulation in human adipose tissue, corroborating the link between LPS-induced inflammation and iron accumulation at the tissue level. In conclusion, our findings demonstrate that induction of adipocyte inflammation disrupts iron homeostasis, resulting in adipocyte iron overload.
Topics: Humans; Lipopolysaccharides; Adipocytes; Adipose Tissue; Inflammation; Iron
PubMed: 37677967
DOI: 10.1016/j.biopha.2023.115428 -
Nutrients Nov 2023Adipose tissue encompasses various types, including White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and beige adipose tissue, each having distinct roles in... (Review)
Review
Adipose tissue encompasses various types, including White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and beige adipose tissue, each having distinct roles in energy storage and thermogenesis. Vitamin D (VD), a fat-soluble vitamin, maintains a complex interplay with adipose tissue, exerting significant effects through its receptor (VDR) on the normal development and functioning of adipocytes. The VDR and associated metabolic enzymes are widely expressed in the adipocytes of both rodents and humans, and they partake in the regulation of fat metabolism and functionality through various pathways. These encompass adipocyte differentiation, adipogenesis, inflammatory responses, and adipokine synthesis and secretion. This review primarily appraises the role and mechanisms of VD in different adipocyte differentiation, lipid formation, and inflammatory responses, concentrating on the pivotal role of the VD/VDR pathway in adipogenesis. This insight furnishes new perspectives for the development of micronutrient-related intervention strategies in the prevention and treatment of obesity.
Topics: Humans; Vitamin D; Adipogenesis; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Obesity; Vitamins; Thermogenesis
PubMed: 38004226
DOI: 10.3390/nu15224832 -
Journal of Advanced Research Jun 2024Adipogenesis, the process of white adipose tissue expansion, plays a critical role in the development of obesity. Osteoprotegerin (OPG), known for its role in bone...
INTRODUCTION
Adipogenesis, the process of white adipose tissue expansion, plays a critical role in the development of obesity. Osteoprotegerin (OPG), known for its role in bone metabolism regulation, emerges as a potential regulator in mediating adipogenesis during obesity onset.
OBJECTIVES
This study aims to elucidate the involvement of OPG in adipogenesis during the early phases of diet-induced obesity and explore its therapeutic potential in obesity management.
METHODS
Using a diet-induced obesity model, we investigated OPG expression patterns in adipocytes and explored the mechanisms underlying its involvement in adipogenesis. We also assessed the effects of targeted silencing of OPG and recombinant OPG administration on obesity progression and insulin resistance. Additionally, the impact of electroacupuncture treatment on OPG levels and obesity management was evaluated in both animal models and human participants.
RESULTS
OPG expression was prominently activated in adipocytes of white adipose tissues during the early phase of diet-induced obesity. Hyperlipidemia induced Cbfa1-dependent OPG transcription, initiating and promoting adipogenesis, leading to cell-size expansion and lipid storage. Intracellular OPG physically bound to RAR and released the PPARɤ/RXR complex, activating adipogenesis-associated gene expression. Targeted silencing of OPG suppressed obesity development, while recombinant OPG administration promoted disease progression and insulin resistance in obese mice. Electroacupuncture treatment suppressed obesity development in an OPG-dependent manner and improved obesity parameters in obese human participants.
CONCLUSION
OPG emerges as a key regulator in mediating adipogenesis during obesity development. Targeting OPG holds promise for the prevention and treatment of obesity, as evidenced by the efficacy of electroacupuncture treatment in modulating OPG levels and managing obesity-related outcomes.
PubMed: 38906326
DOI: 10.1016/j.jare.2024.06.018 -
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 -
International Journal of Molecular... Jul 2023Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid...
Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.
Topics: Animals; Mice; 3T3-L1 Cells; Adipocytes; Adipogenesis; Cell Differentiation; Diabetes Mellitus, Type 2; Lipid Metabolism; Obesity; Proteomics; Transcriptome
PubMed: 37511060
DOI: 10.3390/ijms241411300 -
Nutrients Jul 2023Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main...
Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main characteristic secondary metabolites of RCE are phytoecdysteroids. In order to determine an RCE's phytoecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of RCE and its secondary metabolites on adipogenesis and adipolysis. The evaluation of the anti-adipogenic and lipolytic effects was performed using human Simpson-Golabi-Behmel syndrome cells, where lipid staining and measurement of released glycerol and free fatty acids were employed. The HPTLC method confirmed the presence of 20-hydroxyecdysone (20E), ponasterone A (PA), and turkesterone (TU) in RCE. The observed results revealed that RCE, 20E, and TU significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Moreover, RCE and 20E were found to effectively stimulate basal lipolysis. However, no significant effects were observed with PA and TU applications. Based on our findings, RCE and 20E affect both lipogenesis and lipolysis, while TU only restrains adipogenesis. These results are fundamental for further investigations.
Topics: Humans; Mice; Animals; Adipogenesis; Leuzea; Plant Extracts; Lipid Metabolism; Lipolysis; Lipids; 3T3-L1 Cells
PubMed: 37447387
DOI: 10.3390/nu15133061