Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.009
Filtrar
1.
Am J Physiol Cell Physiol ; 326(4): C1248-C1261, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38581663

RESUMEN

Adipose-derived stem cells (ADSCs) play an important role in the differential capacity for excess energy storage between upper body abdominal (ABD) adipose tissue (AT) and lower body gluteofemoral (GF) AT. We cultured ADSCs from subcutaneous ABD AT and GF AT isolated from eight women with differential body fat distribution and performed single-cell RNA sequencing. Six populations of ADSCs were identified and segregated according to their anatomical origin. The three ADSC subpopulations in GF AT were characterized by strong cholesterol/fatty acid (FA) storage and proliferation signatures. The two ABD subpopulations, differentiated by higher expression of committed preadipocyte marker genes, were set apart by differential expression of extracellular matrix and ribosomal genes. The last population, identified in both depots, was similar to smooth muscle cells and when individually isolated and cultured in vitro they differentiated less than the other subpopulations. This work provides important insight into the use of ADSC as an in vitro model of adipogenesis and suggests that specific subpopulations of GF-ADSCs contribute to the more robust capacity for GF-AT to expand and grow compared with ABD-AT in women.NEW & NOTEWORTHY Identification of distinct subpopulations of adipose-derived stem cells (ADSCs) in upper body abdominal subcutaneous (ABD) and lower body gluteofemoral subcutaneous (GF) adipose tissue depots. In ABD-ADSCs, subpopulations are more committed to adipocyte lineage. GF-ADSC subpopulations are enriched for genes involved in lipids and cholesterol metabolism. Similar depot differences were found in stem cell population identified in freshly isolated stoma vascular fraction. The repertoire of ADSCs subpopulations was different in apple-shaped versus pear-shaped women.


Asunto(s)
Tejido Adiposo , Grasa Subcutánea , Humanos , Femenino , Tejido Adiposo/metabolismo , Adipocitos/metabolismo , Análisis de Secuencia de ARN , Colesterol/metabolismo
2.
Gen Comp Endocrinol ; 352: 114515, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38582177

RESUMEN

Irisin, a myokine identified in 2012, has garnered research interest for its capacity to induce browning of adipocytes and improve metabolic parameters. As such, the potential therapeutic applications of this exercise-induced peptide continue to be explored. Though present across diverse animal species, sequence analysis has revealed subtle variation in the irisin protein. In this review, we consider the effects of irisin on disease states in light of its molecular evolution. We summarize current evidence for irisin's influence on pathologies and discuss how sequence changes may inform development of irisin-based therapies. Furthermore, we propose that the phylogenetic variations in irisin could potentially be leveraged as a molecular clock to elucidate evolutionary relationships.


Asunto(s)
Adipocitos , Fibronectinas , Animales , Fibronectinas/genética , Filogenia , Adipocitos/metabolismo , Evolución Molecular
3.
Nat Commun ; 15(1): 2825, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561362

RESUMEN

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.


Asunto(s)
Dioxigenasas , Leptina , Animales , Humanos , Masculino , Ratones , Adipocitos/metabolismo , Peso Corporal , Dioxigenasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Retroalimentación , Leptina/metabolismo , Mamíferos/metabolismo , Obesidad/genética , Obesidad/metabolismo
4.
Front Immunol ; 15: 1368516, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601146

RESUMEN

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.


Asunto(s)
Proteína HMGB1 , Infarto del Miocardio , Ratones , Animales , Humanos , Interleucina-6/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Retroalimentación , Infarto del Miocardio/metabolismo , Macrófagos/metabolismo , Adipocitos/metabolismo
5.
BMC Genomics ; 25(1): 358, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605318

RESUMEN

BACKGROUND: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. RESULT: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. CONCLUSION: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.


Asunto(s)
Adipocitos , Genes Homeobox , Animales , Bovinos , Adipocitos/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Diferenciación Celular/genética , Proliferación Celular , Factores de Transcripción/metabolismo , Apoptosis/genética , ARN Mensajero/metabolismo , Adipogénesis/genética
6.
Commun Biol ; 7(1): 458, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622242

RESUMEN

Differentiation of adipose progenitor cells into mature adipocytes entails a dramatic reorganization of the cellular architecture to accommodate lipid storage into cytoplasmic lipid droplets. Lipid droplets occupy most of the adipocyte volume, compressing the nucleus beneath the plasma membrane. How this cellular remodeling affects sub-nuclear structure, including size and number of nucleoli, remains unclear. We describe the morphological remodeling of the nucleus and the nucleolus during in vitro adipogenic differentiation of primary human adipose stem cells. We find that cell cycle arrest elicits a remodeling of nucleolar structure which correlates with a decrease in protein synthesis. Strikingly, triggering cytoskeletal rearrangements mimics the nucleolar remodeling observed during adipogenesis. Our results point to nucleolar remodeling as an active, mechano-regulated mechanism during adipogenic differentiation and demonstrate a key role of the actin cytoskeleton in defining nuclear and nucleolar architecture in differentiating human adipose stem cells.


Asunto(s)
Adipogénesis , Citoesqueleto , Humanos , Células Cultivadas , Citoesqueleto/metabolismo , Adipocitos/metabolismo , Gotas Lipídicas/metabolismo
7.
J Transl Med ; 22(1): 363, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632591

RESUMEN

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic-related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/ß-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/ß-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.


Asunto(s)
Adipogénesis , Interleucina-33 , Ratones , Animales , Adipogénesis/genética , Adipocitos/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , beta Catenina/metabolismo , Diferenciación Celular , Obesidad/metabolismo , Vía de Señalización Wnt
8.
Mol Biol Rep ; 51(1): 562, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38644407

RESUMEN

BACKGROUND: Obesity is associated with a wide variety of metabolic disorders that impose significant burdens on patients and society. The "browning" phenomenon in white adipose tissue (WAT) has emerged as a promising therapeutic strategy to combat metabolic disturbances. However, though the anti-diabetic drug dapagliflozin (DAPA) is thought to promote "browning," the specific mechanism of this was previously unclear. METHODS: In this study, C57BL/6 J male mice were used to establish an obesity model by high-fat diet feeding, and 3T3-L1 cells were used to induce mature adipocytes and to explore the role and mechanism of DAPA in "browning" through a combination of in vitro and in vivo experiments. RESULTS: The results show that DAPA promotes WAT "browning" and improves metabolic disorders. Furthermore, we discovered that DAPA activated "browning" through the fibroblast growth factor receptors 1-liver kinase B1-adenosine monophosphate-activated protein kinase signaling pathway. CONCLUSION: These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.


Asunto(s)
Células 3T3-L1 , Tejido Adiposo Blanco , Compuestos de Bencidrilo , Dieta Alta en Grasa , Glucósidos , Ratones Endogámicos C57BL , Obesidad , Proteínas Serina-Treonina Quinasas , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Transducción de Señal , Animales , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Glucósidos/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Compuestos de Bencidrilo/farmacología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos
9.
Cell Death Dis ; 15(4): 285, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653969

RESUMEN

Despite advances in the treatment and care of severe physical injuries, trauma remains one of the main reasons for disability-adjusted life years worldwide. Trauma patients often suffer from disturbances in energy utilization and metabolic dysfunction, including hyperglycemia and increased insulin resistance. White adipose tissue plays an essential role in the regulation of energy homeostasis and is frequently implicated in traumatic injury due to its ubiquitous body distribution but remains poorly studied. Initial triggers of the trauma response are mainly damage-associated molecular patterns (DAMPs) such as histones. We hypothesized that DAMP-induced adipose tissue inflammation contributes to metabolic dysfunction in trauma patients. Therefore, we investigated whether histone release during traumatic injury affects adipose tissue. Making use of a murine polytrauma model with hemorrhagic shock, we found increased serum levels of histones accompanied by an inflammatory response in white adipose tissue. In vitro, extracellular histones induced an inflammatory response in human adipocytes. On the molecular level, this inflammatory response was mediated via a MYD88-IRAK1-ERK signaling axis as demonstrated by pharmacological and genetic inhibition. Histones also induced lytic cell death executed independently of caspases and RIPK1 activity. Importantly, we detected increased histone levels in the bloodstream of patients after polytrauma. Such patients might benefit from a therapy consisting of activated protein C and the FDA-approved ERK inhibitor trametinib, as this combination effectively prevented histone-mediated effects on both, inflammatory gene activation and cell death in adipocytes. Preventing adipose tissue inflammation and adipocyte death in patients with polytrauma could help minimize posttraumatic metabolic dysfunction.


Asunto(s)
Adipocitos , Histonas , Inflamación , Factor 88 de Diferenciación Mieloide , Humanos , Animales , Histonas/metabolismo , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Inflamación/patología , Inflamación/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Muerte Celular/efectos de los fármacos , Masculino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Heridas y Lesiones/complicaciones , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología , Transducción de Señal/efectos de los fármacos
10.
Commun Biol ; 7(1): 492, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654054

RESUMEN

A correlation exists between obstructive sleep apnoea (OSA) and the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), OSA can induce more severe MASLD. However, the underlying regulatory mechanism between the two is unclear. To this end, this study explored the role and possible molecular mechanisms of adipocyte-derived exosomes under OSA in aggravating MASLD. Through sequencing technology, miR-455-3p was identified as a co-differentially expressed miRNA between the MASLD + OSA and Control groups and between the MASLD + OSA and MASLD groups. Upregulation of TCONS-00039830 and Smad2 and downregulation of miR-455-3p in the MASLD and MASLD + OSA groups were validated in vivo and in vitro. TCONS-00039830, as a differentially expressed LncRNA in exosomes found in the sequencing results, transfection notably downregulated miR-455-3p and upregulated Smad2 in hepatocytes. TCONS_00039830 overexpression increased fat, triglyceride and cholesterol levels, while miR-455-3p overexpression decreased these levels. Furthermore, exosome administration promoted the accumulation of fat, triglyceride and cholesterol, upregulated TCONS_00039830 and Smad2, and downregulated miR-455-3p. Overexpression of miR-455-3p reversed the increased fat accumulation and upregulated TCONS_00039830 and Smad2. In conclusion, OSA-derived exosomes promoted hepatocyte steatosis by regulating TCONS_00039830/miR-455-3p/Smad2 axis, thereby aggravating liver damage in MASLD.


Asunto(s)
Exosomas , MicroARNs , Apnea Obstructiva del Sueño , Proteína Smad2 , Animales , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Proteína Smad2/metabolismo , Proteína Smad2/genética , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/complicaciones , Masculino , Ratas , Adipocitos/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Hígado Graso/metabolismo , Hígado Graso/genética , Hígado Graso/patología , Ratas Sprague-Dawley , Humanos , Hepatocitos/metabolismo , Modelos Animales de Enfermedad
11.
Sci Rep ; 14(1): 9018, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641685

RESUMEN

Cyperus rotundus rhizomes have been used in longevity remedies in Thailand for nourishing good health, which led us to investigate the effect on energy homeostasis, especially glucose utilization in myotubes and adipocytes, and on inhibition of lipogenesis in adipocytes. The results showed that an ethyl acetate extract of C. rotundus rhizomes (ECR) containing 1.61%w/w piceatannol, with a half-maximal concentration of 17.76 ± 0.03 µg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, caused upregulation and cell-membrane translocation of glucose transporters GLUT4 and 1 in L6 myotubes but downregulation and cytoplasmic localization of GLUT4 expression in 3T3-L1 adipocytes and was related to the p-Akt/Akt ratio in both cells, especially at 100 µg/mL. Moreover, ECR (25-100 µg/mL) significantly inhibited lipid accumulation via Adenosine Monophosphate-Activated Protein Kinase (AMPK), Acetyl CoA Carboxylase (ACC), and Glycogen Synthase Kinase (GSK) pathways. Its immunoblot showed increased expression of p-AMPKα/AMPKα and p-ACC/ACC but decreased expression of p-Akt/Akt and p-GSK3ß/GSK3ß in 3T3-L1 adipocytes. Moreover, the decreased expression of the adipogenic effectors, perilipin1 and lipoprotein lipase, in ECR-incubated adipocytes (50 and 100 µg/mL) indicated reduced de novo lipogenesis. Our study elucidated mechanisms of C. rotundus that help attenuate glucose tolerance in skeletal muscle and inhibit lipid droplet accumulation in adipose tissue.


Asunto(s)
Cyperus , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Adipogénesis , Glucosa/metabolismo , Adipocitos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Células 3T3-L1
12.
FASEB J ; 38(8): e23613, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38661048

RESUMEN

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.


Asunto(s)
Tejido Adiposo , Macrófagos , PPAR gamma , Rosiglitazona , Trasplante Autólogo , Animales , PPAR gamma/metabolismo , PPAR gamma/genética , Macrófagos/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/citología , Rosiglitazona/farmacología , Masculino , Diferenciación Celular , Adipogénesis , Adipocitos/metabolismo , Ratones , Ratas
13.
Sci Rep ; 14(1): 6656, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509237

RESUMEN

The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma-C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.


Asunto(s)
Adipogénesis , Factores de Transcripción , Ratones , Animales , Factores de Transcripción/metabolismo , Adipogénesis/genética , PPAR alfa/metabolismo , Regulación de la Expresión Génica , Adipocitos/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/genética , PPAR gamma/genética , PPAR gamma/metabolismo , Células 3T3-L1
14.
Sci Rep ; 14(1): 5799, 2024 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461189

RESUMEN

Signal-transducing adaptor protein-2 (STAP-2) is an adaptor molecule involved in several cellular signaling cascades. Here, we attempted to identify novel STAP-2 interacting molecules, and identified c-Cbl associated protein (CAP) as a binding protein through the C-terminal proline-rich region of STAP-2. Expression of STAP-2 increased the interaction between CAP and c-Cbl, suggesting that STAP-2 bridges these proteins and enhances complex formation. CAP/c-Cbl complex is known to regulate GLUT4 translocation in insulin signaling. STAP-2 overexpressed human hepatocyte Hep3B cells showed enhanced GLUT4 translocation after insulin treatment. Elevated levels of Stap2 mRNA have been observed in 3T3-L1 cells and mouse embryonic fibroblasts (MEFs) during adipocyte differentiation. The differentiation of 3T3-L1 cells into adipocytes was highly promoted by retroviral overexpression of STAP-2. In contrast, STAP-2 knockout (KO) MEFs exhibited suppressed adipogenesis. The increase in body weight with high-fat diet feeding was significantly decreased in STAP-2 KO mice compared to WT animals. These data suggest that the expression of STAP-2 correlates with adipogenesis. Thus, STAP-2 is a novel regulatory molecule that controls insulin signal transduction by forming a c-Cbl/STAP-2/CAP ternary complex.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Diferenciación Celular , Insulina , Animales , Humanos , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adipocitos/metabolismo , Fibroblastos/metabolismo , Insulina/metabolismo , Transducción de Señal , Diferenciación Celular/genética
15.
Physiol Rep ; 12(6): e15957, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38546216

RESUMEN

Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT-conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor-alpha (TNF-α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.


Asunto(s)
Fibrilación Atrial , Humanos , Fibrilación Atrial/metabolismo , 60428 , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Inflamación/metabolismo , Pericardio/metabolismo
16.
Cells ; 13(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474425

RESUMEN

Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don't. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence.


Asunto(s)
Cannabis , Endocannabinoides , Humanos , Ratones , Animales , Adolescente , Endocannabinoides/metabolismo , Obesidad/metabolismo , Adipocitos/metabolismo , Receptores de Cannabinoides/metabolismo , Adiposidad
17.
J Oleo Sci ; 73(4): 411-418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38556276

RESUMEN

In 2021, we published three papers related to the anti-inflammatory effects of food ingredients. The present paper reports the effects of vitamin E homologs and sweet basil powder. In these papers, we investigated whether inflammation occurs in the adipose tissue of mice fed a high-fat and high-sucrose diet for 16 weeks. Inflammatory cytokine gene expression was significantly higher in the epididymal fat of the high-fat and high-sucrose diet group than in that of the control diet group. However, the addition of α-tocopherol or δ-tocopherol to the diet could not restrain the inflammation of mice epididymal fats. Thereafter, we investigated the anti-inflammatory effects of α- and δ-tocopherols using the co-cultured cells. Consequently, we clarified that δ-tocopherol inhibited the increase in the gene expressions of inflammatory cytokines. We also examined the effect of sweet basil powder on a similar obese mice model. The final body weight in the high-fat and high-sucrose group that received sweet basil powder was significantly lower than that in the high-fat and high-sucrose diet group. Liver weights were also significantly lower in the high-fat and high-sucrose diet group that received sweet basil powder than in the high-fat and high-sucrose diet group, although adipose tissue weights were unchanged in both groups. Furthermore, sweet basil powder tended to inhibit in lipid synthesis in the mice livers. Therefore, we suggested that sweet basil powder inhibited fatty acid synthesis in mice livers, thereby suppressing liver enlargement, and resulting in body weight loss. Moreover, the gene expression of MCP-1 in the adipose tissue of mice fed a high-fat and high-sucrose diet added with sweet basil powder was significantly lower than that of mice fed a high-fat and high-sucrose diet for 12 weeks. Therefore, sweet basil powder inhibited inflammation onset in the adipose tissue of mice. Taken together, the results suggested that food ingredients, especially vitamin E homologs and sweet basil powder, have anti-inflammatory effects on mice adipose tissue and mice adipocyte-induced inflammation.


Asunto(s)
Ingredientes Alimentarios , Ratones , Animales , Polvos , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Inflamación/genética , Citocinas/metabolismo , Sacarosa , Vitamina E/farmacología , Vitamina E/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL
18.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542331

RESUMEN

Colorectal cancer (CRC) is a major life-threatening disease, being the third most common cancer and a leading cause of death worldwide. Enhanced adiposity, particularly visceral fat, is a major risk factor for CRC, and obesity-associated alterations in metabolic, inflammatory and immune profiles in visceral adipose tissue (VAT) strongly contribute to promoting or sustaining intestinal carcinogenesis. The role of diet and nutrition in obesity and CRC has been extensively demonstrated, and AT represents the main place where diet-induced signals are integrated. Among the factors introduced with diet and processed or enriched in AT, ω3/ω6 polyunsaturated fatty acids (PUFAs) are endowed with pro- or anti-inflammatory properties and have been shown to exert either promoting or protective roles in CRC. In this study, we investigated the impact of ex vivo exposure to the ω3 and ω6 PUFAs docosahexaenoic and arachidonic acids on VAT adipocyte whole transcription in healthy lean, obese and CRC-affected individuals. High-throughput sequencing of protein-coding and long non-coding RNAs allowed us to identify specific pathways and regulatory circuits controlled by PUFAs and highlighted an impaired responsiveness of obese and CRC-affected individuals as compared to the strong response observed in healthy lean subjects. This further supports the role of healthy diets and balanced ω3/ω6 PUFA intake in the primary prevention of obesity and cancer.


Asunto(s)
Neoplasias Colorrectales , Ácidos Grasos Omega-3 , ARN Largo no Codificante , Humanos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Insaturados , Adipocitos/metabolismo , Obesidad/genética , Obesidad/metabolismo , Neoplasias Colorrectales/genética
19.
Medicine (Baltimore) ; 103(13): e37595, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552064

RESUMEN

BACKGROUND: Skin grafting is a common method of treating damaged skin; however, surgical complications may arise in patients with poor health. Currently, no effective conservative treatment is available for extensive skin loss. Mature adipocytes, which constitute a substantial portion of adipose tissue, have recently emerged as a potential source of stemness. When de-lipidated, these cells exhibit fibroblast-like characteristics and the ability to redifferentiate, offering homogeneity and research utility as "dedifferentiated fat cells." METHODS AND RESULTS: We conducted an in vitro study to induce fibroblast-like traits in the adipose tissue by transdifferentiating mature adipocytes for skin regeneration. Human subcutaneous fat tissues were isolated and purified from mature adipocytes that underwent a transformation process over 14 days of cultivation. Microscopic analysis revealed lipid degradation over time, ultimately transforming cells into fibroblast-like forms. Flow cytometry was used to verify their characteristics, highlighting markers such as CD90 and CD105 (mesenchymal stem cell markers) and CD56 and CD106 (for detecting fibroblast characteristics). Administering dedifferentiated fat cells with transforming growth factor-ß at the identified optimal differentiation concentration of 5 ng/mL for a span of 14 days led to heightened expression of alpha smooth muscle actin and fibronectin, as evidenced by RNA and protein analysis. Meanwhile, functional validation through cell sorting demonstrated limited fibroblast marker expression in both treated and untreated cells after transdifferentiation by transforming growth factor-ß. CONCLUSION: Although challenges remain in achieving more effective transformation and definitive fibroblast differentiation, our trial could pave the way for a novel skin regeneration treatment strategy.


Asunto(s)
Desdiferenciación Celular , Transdiferenciación Celular , Humanos , Proyectos Piloto , Desdiferenciación Celular/fisiología , Tejido Adiposo , Adipocitos/metabolismo , Diferenciación Celular , Fibroblastos/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Células Cultivadas
20.
Cell Mol Biol Lett ; 29(1): 45, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553665

RESUMEN

BACKGROUND: Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an antagonist of the glucocorticoid receptor but also an agonist of PPARγ. Therefore, the present study investigated the effect of mifepristone on adipocyte differentiation. METHODS: Mouse 3T3-L1 cells were used as a model for adipocyte differentiation. The lipid droplet formation was evaluated with Bodipy493/503 staining and the expression of adipocyte markers [adiponectin and adipocyte fatty acid binding protein-4 (Fabp4)] was evaluated with quantitative PCR and immunoblot analyses for indication of adipocyte differentiation. siRNA and neutralizing antibodies were used to elucidate the molecular mechanism of mifepristone-induced adipocyte differentiation. Luciferase reporter assay was used to examine the effect of mifepristone on the promoter activity of PPAR-response element (PPRE). The DNA microarray analysis was used to characterize the transcriptome of the mifepristone-induced adipocytes. In vivo adipogenic effect of mifepristone was examined in mice. RESULTS: Mifepristone not only enhanced adipocyte differentiation induced by the conventional protocol consisting of insulin, dexamethasone and 3-isobutyl-1-methylxanthine but also induced adipocyte differentiation alone, as evidenced by lipid droplets formation and induction of the expression of adiponectin and Fabp4. These effects were inhibited by an adiponectin-neutralizing antibody and a PPARγ antagonist. Mifepristone activated the promoter activity of PPRE in a manner sensitive to PPARγ antagonist. A principal component analysis (PCA) of DNA microarray data revealed that the mifepristone-induced adipocytes represent some characteristics of the in situ adipocytes in normal adipose tissues to a greater extent than those induced by the conventional protocol. Mifepristone administration induced an increase in the weight of epididymal, perirenal and gluteofemoral adipose tissues. CONCLUSIONS: Mifepristone alone is capable of inducing adipocyte differentiation in 3T3-L1 cells and adipogenesis in vivo. PPARγ plays a critical role in the mifepristone-induced adipocyte differentiation. Mifepristone-induced adipocytes are closer to the in situ adipocytes than those induced by the conventional protocol. The present study proposes a single treatment with mifepristone as a novel protocol to induce more physiologically relevant adipocytes in 3T3-L1 cells than the conventional protocol.


Asunto(s)
Adiponectina , Mifepristona , Ratones , Animales , Adiponectina/metabolismo , Adiponectina/farmacología , Mifepristona/farmacología , Mifepristona/metabolismo , PPAR gamma/metabolismo , Células 3T3-L1 , Receptores de Glucocorticoides/metabolismo , Diferenciación Celular , Adipogénesis/genética , Adipocitos/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA