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1.
Front Endocrinol (Lausanne) ; 13: 995499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120469

RESUMO

During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT's anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [siPiezo1; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in siPiezo1 cells but not in NC; in contrast, siPiezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.


Assuntos
Adipogenia , Hipertensão , Tecido Adiposo/metabolismo , Animais , Cálcio/metabolismo , Masculino , Mecanorreceptores/metabolismo , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley
2.
Adipocyte ; 11(1): 588-600, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36082406

RESUMO

Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK-ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Tecido Adiposo/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Obesidade/metabolismo , Transdução de Sinais
3.
Stem Cell Res Ther ; 13(1): 443, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056439

RESUMO

BACKGROUND: Bone is a rigid organ that provides physical protection and support to vital organs of the body. Bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors that can differentiate into osteoblasts, adipocytes, and chondrocytes. Cell division cycle 20 (CDC20) is a co-activator of anaphase promoting complex/cyclosome (APC/C), and is required for ubiquitin ligase activity. Our previous study showed that CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we found that knockdown of CDC20 promoted adipogenic differentiation of BMSCs by modulating ß-catenin, which suggested a link between adipogenesis and osteogenesis. METHODS: Lentivirus containing a CDC20 shRNA was used for CDC20 knockdown in human BMSCs (hBMSCs). Primary mouse BMSCs (mBMSCs) were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined using quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting analysis of adipogenic regulators, Oil Red O staining, and transplantation into nude mice. CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR, and western blotting of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Exploration of the molecular mechanism was determined through western blotting, Oil Red O staining, and qRT-PCR. RESULTS: CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. CDC20 knockdown enhanced hBMSC adipogenic differentiation in vitro. CDC20-knockdown hBMSCs showed more adipose tissue-like constructs upon hematoxylin and eosin (H&E) and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in their bone marrow compared with the control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice showed upregulated adipogenic differentiation. Knockdown of CDC20 led to decreased ß-catenin levels, and a ß-catenin pathway activator (lithium chloride) abolished the role of CDC20 in BMSC adipogenic differentiation. CONCLUSIONS: Our findings showed that CDC20 knockdown enhanced adipogenesis of hBMSC and mBMSCs adipogenesis in vitro and in vivo. CDC20 regulates both adipogenesis and osteogenesis of BMSCs, and might lead to the development of new therapeutic targets for "fatty bone" and osteoporosis.


Assuntos
Adipogenia , Proteínas Cdc20/metabolismo , Células-Tronco Mesenquimais , Animais , Medula Óssea/metabolismo , Células da Medula Óssea , Proteínas Cdc20/genética , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Knockout , Camundongos Nus , Osteogênese/genética , beta Catenina/genética , beta Catenina/metabolismo
4.
Medicine (Baltimore) ; 101(36): e30344, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086687

RESUMO

Obesity is characterized by excessive accumulation of adiposity and has been implicated in a strong predisposition to metabolic disorders and cancer, constituting one of the major public health issues worldwide. The formation of new mature adipocytes through differentiation of progenitor or precursor cells during adipogenesis can lead to the expansion of adipose tissue. Recent studies have revealed that the intrinsic risk of obesity arises not only through genetic variants but also through epigenetic predisposition. Enhancer of zeste homolog 2 (EZH2) is an enzymatic catalytic component of polycomb repressive complex 2 that acts as an epigenetic modulator in the regulation of gene expression. EZH2 can modulate the expression of its target genes by the trimethylation of Lys-27 in histone 3 or methylation of non-histone proteins. Emerging evidence has shown the important role played by EZH2 in adipogenesis and obesity. This review provides the latest knowledge about the involvement of EZH2 in the process of adipogenesis and obesity involving adipocyte differentiation, extract key concepts, and highlight open questions toward a better understanding of EZH2 function and the molecular mechanisms underlying obesity.


Assuntos
Adipogenia , Proteína Potenciadora do Homólogo 2 de Zeste , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histonas/metabolismo , Humanos , Obesidade/genética , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo
5.
J Med Chem ; 65(18): 12273-12291, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36074919

RESUMO

The enzyme p300, besides having acetyltransferase activity, can also catalyze other acylation modifications, whose physiological implications are still being investigated. Here, we report that the level of histone butyrylation increases globally as well as locally in the promoters of pro-adipogenic genes during adipogenesis. To delineate the role of p300-catalyzed butyrylation from acetylation in adipogenesis, we identified a semisynthetic derivative (LTK-14A) of garcinol, which specifically inhibited histone butyrylation without affecting acetylation. Treatment of 3T3L1 cells with LTK-14A abolished adipogenesis with downregulation of pro-adipogenic genes along with inhibition of H4K5 butyrylation. Administering LTK-14A to high-fat diet-fed and genetically obese db/db mice led to attenuation/decrease in their weight gain. The reduced obesity could be partially attributed to the inhibition of H4K5 butyrylation in adipocytes and liver. This report therefore not only, for the first time, causally links histone butyrylation with adipogenesis but also presents a probable candidate for anti-obesity therapeutics.


Assuntos
Adipogenia , Fármacos Antiobesidade , Células 3T3-L1 , Acetiltransferases , Acilação , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Catálise , Dieta Hiperlipídica , Histonas/metabolismo , Camundongos , Obesidade/tratamento farmacológico
6.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077381

RESUMO

Although significant advancement has been made in the study of adipogenesis, knowledge about how chromatin accessibility regulates yak adipogenesis is lacking. We here described genome-wide dynamic chromatin accessibility in preadipocytes and adipocytes by using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), and thus revealed the unique characteristics of open chromatin during yak adipocyte differentiation. The chromatin accessibility of preadipocytes and adipocytes exhibited a similar genomic distribution, displaying a preferential location within the intergenic region, intron, and promoter. The pathway enrichment analysis identified that genes with differential chromatin accessibility were involved in adipogenic metabolism regulation pathways, such as the peroxisome proliferator activated receptor-γ (PPAR) signaling pathway, wingless-type MMTV integration site (Wnt) signaling pathway, and extracellular matrix-receptor (ECM-receptor) interaction. Integration of ATAC-seq and mRNA-seq revealed that genes with a high expression were associated with high levels of chromatin accessibility, especially within 1 kb upstream and downstream of the transcription start site. In addition, we identified a series of transcription factors (TFs) related to adipogenesis and created the TF regulatory network, providing the possible interactions between TFs during yak adipogenesis. This study is crucial for advancing the understanding of transcriptional regulatory mechanisms of adipogenesis and provides valuable information for understanding the adaptation of plateau species to high-altitude environments by maintaining whole body homeostasis through fat metabolism.


Assuntos
Adipogenia , Cromatina , Adipócitos/metabolismo , Adipogenia/genética , Animais , Bovinos , Cromatina/genética , Cromatina/metabolismo , Sequenciamento de Cromatina por Imunoprecipitação , Sequenciamento de Nucleotídeos em Larga Escala
7.
Artigo em Inglês | MEDLINE | ID: mdl-36078578

RESUMO

BACKGROUND: Recent studies suggested that individuals with metabolic disorders have altered function of adipocytes and adipose stem cell subpopulations, which impairs tissue homeostasis, promoting insulin resistance and diabetes development. The non-psychoactive phytocannabinoid CBD was found to modulate adipose tissue metabolism, however, its exact role in controlling ASCs' fate is still poorly understood. OBJECTIVES: This investigation aimed to elucidate whether pretreatment of ASCs with CBD can protect against ER stress development and maintain the cytophysiological properties of cells. METHODS: Human ASCs were cultured under control and adipogenic conditions. Prior to the experiments, cells in the experimental group were pretreated with CBD following the addition of an ER stress inducer-tunicamycin. After the experiments, the cells were subsequently tested for expression of the apoptotic, ER stress, and anti-inflammatory-related genes using RT-qPCR. Oxidative stress was analysed with flow cytometric assays. RESULTS: Cells pretreated with CBD displayed decreased apoptosis and enhanced proliferation rate. Additionally, the expression of pro-inflammatory cytokines and miRNAs was significantly reduced. The obtained results also demonstrated an obvious reduction in intracellular accumulated ROS and NO, as well as mitigated ER stress through the down-regulation of IRE-1, PERK, CHOP, and ATF6 transcripts upon CBD treatment. CONCLUSION: The presented data provide the evidence that CBD protects ASCs against ER stress development and its complications and, thus, offers new insights for the management of obesity through the regulation of adipose tissue dynamics.


Assuntos
Canabidiol , Células-Tronco Mesenquimais , Adipogenia , Tecido Adiposo , Canabidiol/farmacologia , Estresse do Retículo Endoplasmático , Humanos
8.
Commun Biol ; 5(1): 927, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36071206

RESUMO

Cultured meat can provide a sustainable and more ethical alternative to conventional meat. Most of the research in this field has been focused on developing muscle tissue, as it is the main component of meat products, while very few studies address cultured fat tissue, an essential component in the human diet and determinant of meat quality, flavor, juiciness, and tenderness. Here, we engineered bovine fat tissue for cultured meat and incorporated it within engineered bovine muscle tissue. Mesenchymal stem cells (MSCs) were derived from bovine adipose tissue and exhibited the typical phenotypic profile of adipose-derived MSCs. MSC adipogenic differentiation and maturation within alginate-based three-dimensional constructs were optimized to yield a fat-rich edible engineered tissue. Subsequently, a marble-like construct, composed of engineered bovine adipose and muscle tissues, was fabricated, mimicking inter- and intra-muscular fat structures.


Assuntos
Carbonato de Cálcio , Células-Tronco Mesenquimais , Adipogenia , Tecido Adiposo , Animais , Bovinos , Humanos , Carne
9.
Biomed Pharmacother ; 154: 113629, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36058150

RESUMO

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine due to its strong phytochemical profile and pharmacological efficacy. In this study, we evaluated the anti-obesity potential of Pyrus ussuriensis Maxim extracts (PUE) and investigated the underlying mechanisms using a combination of in vitro, in vivo, and microbiota regulation approaches. In an adipogenesis assay, the fermented (F)PUE and non-fermented (NF)PUE significantly reduced the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 85.33 and 96.67 µg/mL, respectively. In a high-fat diet (HFD)-induced obese rat model (n = 8 animals/group), oral administration of FPUE additionally reduced the total body weight gain significantly. No difference in food intake was observed, however, between the control-chow diet, FPUE, and NFPUE-treated HFD rats. Adipose tissue mass and systemic insulin resistance were markedly reduced in FPUE-treated HFD rats, in a dose-dependent manner. Treatment with FPUE also greatly improved obesity-related biomarkers, including total cholesterol, leptin, active ghrelin, Total GIP, adiponectin, and proinflammatory cytokines. Moreover, FPUE significantly suppressed HFD-induced adipogenic genes expression, while increasing fatty acid oxidation-related genes expression. Additionally, FPUE treatment attenuated the HFD-induced Firmicutes proportion within the intestinal microbiota by regulating key metabolic pathways, thus enhancing microbial population diversity (e.g., increasing Bacteroides, Bifidobacterium, Prevotella, Eubacterium, and Clostridium). Together, these results reveal a strong anti-obesity potential of FPUE through adipogenesis, lipid metabolism, weight reduction, and microbiota regulation, raising the possibility of developing FPUE as a novel therapeutic agent to control obesity and obesity-associated metabolic disorders.


Assuntos
Fármacos Antiobesidade , Microbiota , Pyrus , Células 3T3-L1 , Adipogenia , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
10.
J Vis Exp ; (186)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35993709

RESUMO

Primary preadipocytes are a valuable experimental system for understanding the molecular pathways that control adipocyte differentiation and metabolism. Chicken embryos provide the opportunity to isolate preadipocytes from the earliest stage of adipose development. This primary cell can be used to identify factors influencing preadipocyte proliferation and adipogenic differentiation, making them a valuable model for studies related to childhood obesity and control of excess fat deposition in poultry. The rapid growth of postnatal adipose tissue effectively wastes feed by allocating it away from muscle growth in broiler chickens. Therefore, methods to understand the earliest stages of adipose tissue development may provide clues to regulate this tendency and identify ways to limit adipose expansion early in life. The present study was designed to develop an efficient method for isolation, primary culture, and adipogenic differentiation of preadipocytes isolated from developing adipose tissue of commercial broiler (meat-type) chick embryos. The procedure has been optimized to yield cells with high viability (~98%) and increased capacity to differentiate into mature adipocytes. This simple method of embryonic preadipocyte isolation, culture, and differentiation supports functional analyses of fat growth and development in early life.


Assuntos
Adipócitos , Obesidade Pediátrica , Adipogenia , Tecido Adiposo , Animais , Diferenciação Celular , Embrião de Galinha , Galinhas/metabolismo
11.
EMBO J ; 41(18): e108206, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35996853

RESUMO

Adipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations, including the enigmatic CD142+ cells. An outstanding challenge is to functionally characterise this population, as discrepant properties, from adipogenic to non- and anti-adipogenic, have been reported for these cells. To resolve these phenotypic ambiguities, we characterised mammalian subcutaneous CD142+ ASPCs across various experimental conditions, demonstrating that CD142+ ASPCs exhibit high molecular and phenotypic robustness. Specifically, we find these cells to be firmly non- and anti-adipogenic both in vitro and in vivo, with their inhibitory signals also impacting adipogenic human cells. However, these CD142+ ASPC-specific properties exhibit surprising temporal phenotypic alterations, and emerge only in an age-dependent manner. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142- ASPCs into a non-adipogenic, Areg-like state.


Assuntos
Adipogenia , Tretinoína , Adipócitos/metabolismo , Tecido Adiposo , Anfirregulina/metabolismo , Animais , Diferenciação Celular , Humanos , Mamíferos , Transdução de Sinais , Tretinoína/farmacologia
12.
Cells ; 11(16)2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-36010568

RESUMO

Osteoporosis, or steroid-induced osteonecrosis of the hip, is accompanied by increased bone marrow adipogenesis. Such a disorder of adipogenic/osteogenic differentiation, affecting bone-marrow-derived mesenchymal stem cells (BMSCs), contributes to bone loss during aging. Here, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on the osteogenic and adipogenic differentiation capacity of naïve (undifferentiated) hBMSCs. We observed that all EV groups increased viability and proliferation capacity and suppressed the apoptosis of naïve hBMSCs. In particular, EVs derived from hBMSCs at late-stage osteogenic differentiation promoted the osteogenic potential of naïve hBMSCs more effectively than EVs derived from naïve hBMSCs (naïve EVs), as indicated by the increased gene expression of COL1A1 and OPN. In contrast, the adipogenic differentiation capacity of naïve hBMSCs was inhibited by treatment with EVs from osteogenic differentiated hBMSCs. Proteomic analysis revealed that osteogenic EVs and naïve EVs contained distinct protein profiles, with pro-osteogenic and anti-adipogenic proteins encapsulated in osteogenic EVs. We speculate that osteogenic EVs could serve as an intercellular communication system between bone- and bone-marrow adipose tissue, for transporting osteogenic factors and thus favoring pro-osteogenic processes. Our data may support the theory of an endocrine circuit with the skeleton functioning as a ductless gland.


Assuntos
Vesículas Extracelulares , Osteogênese , Adipogenia , Diferenciação Celular , Humanos , Proteômica
13.
Sci Rep ; 12(1): 13582, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945422

RESUMO

Fibro-adipogenic progenitors (FAPs) are essential in supporting regeneration in skeletal muscle, but in muscle pathologies FAPs the are main source of excess extracellular matrix (ECM) resulting in fibrosis. Fibrotic ECM has altered mechanical and architectural properties, but the feedback onto FAPs of stiffness or ECM properties is largely unknown. In this study, FAPs' sensitivity to their ECM substrate was assessed using collagen coated polyacrylamide to control substrate stiffness and collagen hydrogels to engineer concentration, crosslinking, fibril size, and alignment. FAPs on substrates of fibrotic stiffnesses had increased myofibroblast activation, depicted by αSMA expression, compared to substrates mimicking healthy muscle, which correlated strongly YAP nuclear localization. Surprisingly, fibrosis associated collagen crosslinking and larger fibril size inhibited myofibroblast activation, which was independent of YAP localization. Additionally, collagen crosslinking and larger fibril diameters were associated with decreased remodeling of the collagenous substrate as measured by second harmonic generation imaging. Inhibition of YAP activity through verteporfin reduced myofibroblast activation on stiff substrates but not substrates with altered architecture. This study is the first to demonstrate that fibrotic muscle stiffness can elicit FAP activation to myofibroblasts through YAP signaling. However, fibrotic collagen architecture actually inhibits myofibroblast activation through a YAP independent mechanism. These data expand knowledge of FAPs sensitivity to ECM and illuminate targets to block FAP's from driving progression of muscle fibrosis.


Assuntos
Adipogenia , Miofibroblastos , Diferenciação Celular , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibrose , Humanos , Músculo Esquelético/metabolismo , Miofibroblastos/patologia
14.
Cells ; 11(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35954183

RESUMO

Genetic improvement of pork quality is one of the hot topics in pig germplasm innovation. Backfat thickness and intramuscular fat content are important indexes of meat quality. MiRNAs are becoming recognized as a crucial regulator of adipose development. Therefore, it is crucial to understand how miR-23b regulates fat metabolism at the molecular level. In the present study, Oil Red O staining, and Western blot were used to evaluate the effect of miR-23b on the differentiation of porcine preadipocytes. Dual-luciferase reporter gene assay, pulldown, and RIP were used to reveal the mechanism of miR-23b regulating cell differentiation. The findings demonstrated that miR-23b promotes the expression of adipogenic factors and increases the content of lipid droplets, thus promoting the differentiation of preadipocytes. Further research found that miR-23b can directly bind to the 3'UTR of SESN3 to regulate adipogenic differentiation. In addition, it was speculated that miR-23b controls cell differentiation by positively regulating the expression of ACSL4 in other ways. Here, we demonstrate that miR-23b promotes the differentiation of porcine preadipocytes by targeting SESN3 and promoting the expression of ACSL4. The present study is meaningful to the improvement of pork quality and the development of animal husbandry.


Assuntos
Adipócitos , MicroRNAs , Regiões 3' não Traduzidas/genética , Adipócitos/metabolismo , Adipogenia/genética , Animais , Diferenciação Celular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Suínos
15.
Cells ; 11(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35954201

RESUMO

The obesity epidemic represents a critical public health issue worldwide, as it is a vital risk factor for many diseases, including type 2 diabetes (T2D) and cardiovascular disease. Obesity is a complex disease involving excessive fat accumulation. Proper adipose tissue accumulation and function are highly transcriptional and regulated by many genes. Recent studies have discovered that post-transcriptional regulation, mainly mediated by RNA-binding proteins (RBPs), also plays a crucial role. In the lifetime of RNA, it is bound by various RBPs that determine every step of RNA metabolism, from RNA processing to alternative splicing, nucleus export, rate of translation, and finally decay. In humans, it is predicted that RBPs account for more than 10% of proteins based on the presence of RNA-binding domains. However, only very few RBPs have been studied in adipose tissue. The primary aim of this paper is to provide an overview of RBPs in adipogenesis and adipose function. Specifically, the following best-characterized RBPs will be discussed, including HuR, PSPC1, Sam68, RBM4, Ybx1, Ybx2, IGF2BP2, and KSRP. Characterization of these proteins will increase our understanding of the regulatory mechanisms of RBPs in adipogenesis and provide clues for the etiology and pathology of adipose-tissue-related diseases.


Assuntos
Adipogenia , Diabetes Mellitus Tipo 2 , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Humanos , Obesidade/genética , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo
16.
Sheng Wu Gong Cheng Xue Bao ; 38(8): 2939-2947, 2022 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-36002422

RESUMO

The aim of this study was to investigate the effect of activating transcription factor 3 (ATF3) on the differentiation of intramuscular preadipocytes in goat, and to elucidate its possible action pathway at the molecular level. In this study, the recombinant plasmid of goat pEGFP-N1-ATF3 was constructed, and the intramuscular preadipocytes were transfected with liposomes. The relative expression levels of adipocyte differentiation marker genes were detected by quantitative real-time PCR (qRT-PCR). After transfection of goat intramuscular preadipocytes with the goat pEGFP-N1-ATF3 overexpression vector, it was found that the accumulation of lipid droplets was inhibited, and the adipocyte differentiation markers PPARγ, C/EBPα and SREBP1 were extremely significantly down-regulated (P < 0.01), while C/EBPß and AP2 were significantly down-regulated (P < 0.05). The ATF3 binding sites were predicted to exist in the promoter regions of PPARγ, C/EBPα and AP2 by the ALGGEN PROMO program. The overexpression of goat ATF3 inhibits the accumulation of lipid droplets in intramuscular preadipocytes, and this effect may be achieved by down-regulating PPARγ, C/EBPα and AP2. These results may facilitate elucidation of the regulatory mechanism of ATF3 in regulating the differentiation of goat intramuscular preadipocytes.


Assuntos
Fator 3 Ativador da Transcrição , PPAR gama , Células 3T3-L1 , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/farmacologia , Adipócitos , Adipogenia/genética , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/farmacologia , Diferenciação Celular , Cabras , Camundongos , PPAR gama/genética , PPAR gama/metabolismo
17.
Compr Physiol ; 12(4): 1-13, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950657

RESUMO

Adipose tissue contains resident B lymphocytes (B cells) with varying immune functions and mechanisms, depending on the adipose depot type and location. The heterogeneity of B cells and their functions affect the immunometabolism of the adipose tissue in aging and age-associated metabolic disorders. B cells exist in categorizations of subsets that have developmental or phenotypic differences with varying functionalities. Subsets can be categorized as either protective or pathogenic depending on their secretion profile or involvement in metabolic maintenance. In this article, we summarized recent finding on the B cell heterogeneity and discuss how we can utilize our current knowledge of adipose resident B lymphocytes for potential treatment for age-associated metabolic disorders. © 2022 American Physiological Society. Compr Physiol 12: 1-13, 2022.


Assuntos
Subpopulações de Linfócitos B , Doenças Metabólicas , Adipogenia , Tecido Adiposo/metabolismo , Envelhecimento/metabolismo , Humanos , Doenças Metabólicas/metabolismo
18.
Cell Mol Life Sci ; 79(9): 488, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984564

RESUMO

An imbalance of human mesenchymal stem cells (hMSCs) adipogenic and osteogenic differentiation is crucial in the pathogenesis of osteoporosis, and elucidation of the underlying mechanism is urgently needed. APPL1, an adaptor protein of the adiponectin receptor, was recently shown to be closely related to bone mass. However, the role of APPL1 in the imbalance of hMSC differentiation in osteoporosis is unclear. Therefore, we aimed to explore the mechanisms by which APPL1 alters hMSCs adipogenic differentiation in osteoporosis. Here, we found that APPL1 expression was downregulated in elderly patients with osteoporosis and in mouse osteoporosis model. APPL1 negatively regulated hMSC adipogenic differentiation in vivo and in vitro. Mechanistically, by enhancing ubiquitination-mediated Myoferlin degradation, downregulated APPL1 expression increased the risk of lysosome dysfunction during hMSCs adipogenic differentiation. Lysosomal dysfunction inhibited autophagy flux by suppressing autophagosome degradation and promoted hMSC differentiation towards the adipocyte lineage. Our findings suggest that APPL1/Myoferlin downregulation promoted hMSCs adipogenic differentiation by inhibiting autophagy flux, further impairing the balance of hMSCs adipogenic and osteogenic differentiation in osteoporosis; the APPL1/ Myoferlin axis may be a promising diagnostic and therapeutic target for osteoporosis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Membrana , Células-Tronco Mesenquimais , Proteínas Musculares , Osteoporose , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipogenia/genética , Idoso , Animais , Autofagia/fisiologia , Proteínas de Ligação ao Cálcio , Diferenciação Celular/fisiologia , Células Cultivadas , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteínas Musculares/metabolismo , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo
19.
Genes (Basel) ; 13(8)2022 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-36011355

RESUMO

(1) Background: Adipogenesis is an important issue in human health and livestock meat quality that has received widespread attention and extensive study. However, alternative splicing events may generate multiple isoforms with different functions. This will lead to known knowledge being far more complex than before. (2) Methods: We studied the effects of two different TUSC5 isoforms (TUSC5A and TUSC5B) in cattle on adipogenesis by constructing over-expression cell models and RNA-sequencing methods. (3) Results: We discovered that over-expression of TUSC5A promotes the process of adipogenesis while over-expression of TUSC5B suppresses it. Eight important genes (PPARG, ACC1, FASN, SCD1, LPL, FABP4, GPDH, and GLUT4) during adipogenesis were significantly promoted (student's t-test, p < 0.05) by TUSC5A and suppressed by TUSC5B both before and after cell differentiation. By performing a comprehensive analysis using a RNA-seq strategy, we found that both up-regulated differentially expressed genes (DEGs, |log2FoldChange| ≥ 1, p ≤ 0.05) of TUSC5A and down-regulated DEGs of TUSC5B were significantly enriched in the adipogenesis related GO terms, and the PPAR signaling pathway may play important role in those differences. (4) Conclusions: Our study proved that over-expression of two TUSC5 isoforms would regulate adipogenesis in the opposite direction. It is important to understand the function of the TUSC5 gene correctly.


Assuntos
Adipócitos , Adipogenia , Proteínas de Membrana/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adipócitos/metabolismo , Adipogenia/genética , Animais , Bovinos/genética , Diferenciação Celular/genética , Humanos , PPAR gama/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
20.
Genes (Basel) ; 13(8)2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-36011378

RESUMO

Adipogenesis is a complex and precisely orchestrated process mediated by a series of adipogenic regulatory factors. Recent studies have highlighted the importance of microRNAs (miRNAs) in diverse biological processes, most specifically in regulating cell differentiation and proliferation. However, the mechanisms of miRNAs in adipogenesis are largely unknown. In this study, we found that miR-107 expression was higher in bovine adipose tissue than that in other tissues, and there was a downregulation trend during adipocyte differentiation. To explore the function of miR-107 in adipocyte differentiation, agomiR-107 and antiagomiR-107 were transfected into bovine adipocytes, respectively. Oil Red O staining, CCK-8, EdU assays, RT-qPCR, and Western blotting were performed, and the results showed that overexpressed miR-107 significantly suppressed fat deposition and adipocyte differentiation, while knockdown of miR-107 promoted fat deposition and adipocytes differentiation. In addition, through bioinformatics analysis, luciferase reporter assays, RT-qPCR, and Western blotting, we identified apolipoprotein 2 (APOC2) as a target of miR-107. Transfection of siRNA-APOC2 into adipocytes led to suppression in adipocyte differentiation and proliferation, suggesting a positive role of APOC2 in bovine lipogenesis. In summary, our findings suggested that miR-107 regulates bovine adipocyte differentiation and lipogenesis by directly targeting APOC2, and these results. These theoretical and experimental basis for future clarification of the regulation mechanism of adipocyte differentiation and lipogenesis. Moreover, for the highly conserved among different species, miR-107 may be a potential molecular target to be used for the treatment of lipid-related diseases in the future.


Assuntos
Adipogenia , MicroRNAs , Adipócitos/metabolismo , Adipogenia/genética , Animais , Apolipoproteína C-II/metabolismo , Bovinos , Diferenciação Celular/genética , MicroRNAs/genética , MicroRNAs/metabolismo
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