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1.
Life Sci ; 254: 117768, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407840

RESUMO

AIMS: In this study, we used a cross-junction microfluidic device for preparation of alendronate-loaded chitosan nanoparticles with desired characteristics to introduce a suitable element for bone tissue engineering scaffolds. MAIN METHODS: By controlling the reaction condition in microfluidic device, six types of alendronate-loaded chitosan nanoparticles were fabricated which had different physical properties. Hydrodynamic diameter of synthetized particles was evaluated by dynamic light scattering (102 to 215 nm). Nanoparticle morphology was determined by SEM and AFM images. The osteogenic effects of prepared selected nanoparticles on human adipose stem cells (hA-MSCs) were evaluated by assessment of alkaline phosphatase (ALP) activity, calcium deposition, ALP and osteopontin gene expression. KEY FINDINGS: The highest loading efficiency percentage (%LE) was %32.42 ± 2.02. Based on MTT assessment, two samples which had no significant cytotoxicity were chosen for further studies (particle sizes and %LE were 142 ± 6.1 nm, 198 ± 16.56 nm, %16.76 ± 3.91 and %32.42 ± 2.02, respectively). In vitro release behavior of nanoparticles displayed pH responsive characteristics. Significant faster release was seen in acidic pH = 5.8 than neutral pH = 7.4. The selected nanoparticles demonstrated higher ALP activity at 14 days in comparison to selected blank sample and osteogenic differentiation media (ODM) and a downregulation at 21 days in comparison to 14 days. Calcium content assay at 21 days displayed significant differences between alendronate-loaded nanoparticles and ODM. ALP and osteopontin mRNA expression was significantly higher than the cells cultured in ODM at 14 and 21 days. SIGNIFICANCE: We concluded that our prepared nanoparticles significantly enhanced osteogenic differentiation of hA-MSCs and can be a suitable compartment of bone tissue engineering scaffolds.


Assuntos
Alendronato/metabolismo , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/instrumentação , Adipócitos , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quitosana/metabolismo , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Microfluídica/métodos , Nanopartículas , Células-Tronco/efeitos dos fármacos , Engenharia Tecidual/métodos , Tecidos Suporte
4.
Life Sci ; 254: 117786, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32433918

RESUMO

AIMS: Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model. MAIN METHODS: OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw., i.p., twice a week), or IL-12 (300 ng/kg bw., i.p., one a week) for 60 days, or both P-MAPA and IL-12. Immunohistochemistry, western blot, flow cytometry, and multiplex assay were used to examine the effectiveness of immunotherapies in OC. KEY FINDINGS: The combinatory therapy improved the general OC features, reducing inflammatory cells and adipocyte accumulation, in addition to revealing a soft and mobile tissue with no adherences and peritoneal implants. P-MAPA treatment increased the levels of TLR2, TLR4 and TRIF in OCs while decreasing the number of regulatory T (Treg) cells. Additionally, the association of P-MAPA with IL-12 significantly increased the number of CD4+ and CD8+ T effector cells in draining lymph nodes. Regarding the inflammatory mediators, P-MAPA enhanced the levels of the pro-inflammatory cytokine IL-17 while P-MAPA+IL-12 increased the levels of IL-1ß. Treatment with IL-12 enhanced the cytokine levels of IL-17, TNF-α, IL-1ß, and IL-2 in addition to the chemokine MIP-1α. SIGNIFICANCE: We conclude that P-MAPA upregulated TLR2 and TLR4 signaling, possibly activating the non-canonical pathway, while attenuating the tumor immunosuppression. Also, the combination of P-MAPA with IL-12 improves the antitumor immunoresponse, opening a new therapeutic approach for fighting OC.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-12/farmacologia , Ácidos Linoleicos/farmacologia , Ácidos Oleicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Adipócitos/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CCL3/metabolismo , Citocinas/metabolismo , Sinergismo Farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-12/uso terapêutico , Ácidos Linoleicos/uso terapêutico , Ácidos Oleicos/uso terapêutico , Neoplasias Ovarianas/induzido quimicamente , Neoplasias Ovarianas/metabolismo , Ratos , Linfócitos T Reguladores/efeitos dos fármacos
5.
Chemosphere ; 253: 126772, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464760

RESUMO

Zeranol is an approved but controversial growth-promoting agent for livestock in North America. It is a mycotoxin metabolite secreted by the Fusarium family fungi. The regulatory bodies in this region have established the acceptable daily intake and exposure below the level would not significantly increase the health risk for humans. However, their European counterparts have yet to establish an acceptable level and do not permit the use of this agent in farm animals. Given the growth-promoting ability of zeranol, its effect on energy metabolism was investigated in the current study. Our results indicated that zeranol could induce glucose transporter type 4 (GLUT4) expression in 3T3 L1 cells at 10 µM and initiate the translocation of the glucose transporter to the membrane as assayed by confocal microscopy. The translocation was likely triggered by the increase of GLUT4 and p-Akt. The insulin signal transduction pathway of glucose translocation was analyzed by Western blot analysis. Since no increase in the phosphorylated insulin receptor substrate in zeranol-treated cells was evidenced, the increased p-Akt and GLUT4 amount should be the mechanism dictating the GLUT4 translocation. In summary, this study showed that zeranol could perturb glucose metabolism in differentiated 3T3 L1 adipocytes. Determining the growth-promoting mechanism is crucial to uncover an accepted alternative to the general public.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Reguladores de Crescimento de Planta/toxicidade , Zeranol/toxicidade , Células 3T3-L1 , Adipócitos , Animais , Antígenos CD , Metabolismo dos Carboidratos , Glucose/metabolismo , Insulina/metabolismo , Gado , Camundongos , América do Norte , Fosforilação , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
DNA Cell Biol ; 39(7): 1119-1126, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32379499

RESUMO

Sirtuin 2 (Sirt2) belongs to the NAD+-dependent deacetylase family, is more highly expressed than other family members in adipocytes, and plays crucial roles in a wide range of biological processes. However, the mechanisms underlying Sirt2 expression during adipogenesis are poorly studied. In this study, the transcriptional start site (TSS) of Sirt2 was identified and two alternative transcript variants were spliced from Sirt2. The 5'-regulatory region of Sirt2 was also characterized; no TATA-box or CCAAT-box was presented in the 5'-flanking region. Two cytosine-phosphate diester-guanine (CpG) islands were also identified between nucleotides -563 and +4. A dual-luciferase reporter assay revealed that a 178 base pair sequence upstream from the TSS (+1) was the core promoter of Sirt2. Results from a site-directed mutagenesis experiment, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay indicated Yin Yang 1 (YY1) to be a positive regulator of bovine Sirt2 in preadipocytes. YY1 is likely to suppress adipogenesis in two different ways by regulating peroxisome proliferator-activated receptor gamma expression. Our results expand the information on the regulatory network of adipogenesis, which is an important basis for improving beef quality, treating obesity, and other related diseases.


Assuntos
Adipócitos/metabolismo , Sirtuína 2/genética , Ativação Transcricional , Fator de Transcrição YY1/metabolismo , Células 3T3-L1 , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Humanos , Camundongos , Regiões Promotoras Genéticas/genética , Fator de Transcrição YY1/química
7.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 122-127, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32314882

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of porcine acellular cartilaginous matrix (pACM) on the proliferation and differentiation of human adipose-derived stromal cells (hADSCs). METHODS: pACM was prepared from porcine articular cartilage through decellularization treatment. hADSCs were isolated from human adipose tissues and cultured with different pACM concentrations. No pACM was used as the control group. The effect of pACM on hADSCs proliferation was detected by CCK-8 method. Moreover, the effect of pACM on hADSCs chondrogenic differentiation was analyzed through fluorescence quantitative polymerase chain reaction and Western blot. RESULTS: hADSCs proliferation rate in 0.5, 1.0, and 2.0 mg·mL⁻¹ pACM groups was not significantly different from that in the control group, whereas that in 4.0 and 8.0 mg·mL⁻¹ pACM group was lower than that in the control group (P<0.05). The expression levels of pACM chondrogenic genes, including SOX-9, collagen type Ⅱ alpha 1 chain (COL2A1), and aggrecan (ACAN) and cell adhesion-related gene LAMININ in 0.5, 1.0, and 2.0 mg·mL⁻¹ pACM group were higher than those of the control group (P<0.05), but that of a stemness-related gene Notch-1 was lower than that of the control group (P<0.05). No statistical difference was found in the expression of a lipogenesis-related gene peroxisome proliferator-activated receptor-γ (PPAr-γ) (P>0.05). The expression levels of chondrogenic proteins (SOX-9, COL2A1, and ACAN) were higher than those of the control group (P<0.05). CONCLUSIONS: Appropriate pACM con-centrations do not affect hADSCs proliferation but can induce hADSCs chondrogenic differentiation.


Assuntos
Adipócitos , Células-Tronco , Tecido Adiposo , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrogênese , Humanos , Células Estromais , Suínos
8.
Obesity (Silver Spring) ; 28(7): 1187-1190, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32339391

RESUMO

Coronavirus disease-2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis. In this Perspective, we argue that adipocytes and adipocyte-like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to SARS-CoV-2. Expression of angiotensin-converting enzyme 2 (the functional receptor for SARS-CoV) is upregulated in adipocytes of patients with obesity and diabetes, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID-19 infections. Similar to the recently established adipocyte-myofibroblast transition, pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of pulmonary fibrosis. This may significantly increase the severity of the local response to SARS-CoV-2 in the lung. To reduce the severity and mortality associated with COVID-19, we propose to probe for the clinical response to thiazolidinediones, peroxisome proliferator activated receptor γ agonists that are well-known antidiabetic drugs. Thiazolidinediones are able to stabilize lipofibroblasts in their "inactive" state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.


Assuntos
Adipócitos/virologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia
9.
Nat Commun ; 11(1): 1730, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265443

RESUMO

Cold stimuli and the subsequent activation of ß-adrenergic receptor (ß-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the ß3-AR pathway inevitably increases blood pressure, a significant risk factor for cardiovascular disease, and, thus, limits its application for the treatment of obesity. To activate fat thermogenesis under tight spatiotemporal control without external stimuli, here, we report an implantable wireless optogenetic device that bypasses the ß-AR pathway and triggers Ca2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca2+ cycling fat thermogenesis and increases whole-body energy expenditure without cold stimuli. Significantly, the light-induced fat thermogenesis was sufficient to protect mice from diet-induced body-weight gain. The present study provides the first proof-of-concept that fat-specific cold mimetics via activating non-canonical thermogenesis protect against obesity.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Channelrhodopsins/metabolismo , Obesidade/terapia , Optogenética/instrumentação , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Termogênese/efeitos da radiação , Adipócitos/efeitos da radiação , Tecido Adiposo/efeitos da radiação , Animais , Peso Corporal/fisiologia , Peso Corporal/efeitos da radiação , Cálcio/metabolismo , Células Cultivadas , Channelrhodopsins/efeitos da radiação , Channelrhodopsins/uso terapêutico , Dieta , Metabolismo Energético/efeitos da radiação , Locomoção , Masculino , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Optogenética/métodos , Consumo de Oxigênio , Receptores Adrenérgicos beta/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Termogênese/fisiologia
10.
Sheng Li Xue Bao ; 72(2): 175-180, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328611

RESUMO

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.


Assuntos
Adipócitos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Leptina/metabolismo , Células 3T3 , Adenilato Quinase , Animais , Regulação para Baixo , Sistema de Sinalização das MAP Quinases , Camundongos , Fosforilação , Transdução de Sinais
11.
PLoS One ; 15(4): e0231796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287314

RESUMO

BACKGROUND: Antimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients. METHODS: Serum samples from normal and IBD patients were collected from two UCLA cohorts. Surgical resection samples of human colonic and mesenteric fat tissues from IBD and non-IBD (colon cancer) patients were collected from Cedars-Sinai Medical Center. RESULTS: High serum elafin levels were associated with a significantly elevated risk of intestinal stricture in Crohn's disease (CD) patients. Microsoft Azure Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlations with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index), but not endoscopic disease activity (Mayo Endoscopic Subscore and Simple Endoscopic Index for CD) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels. Colonic elafin mRNA and protein expression were not associated with clinical disease activity and histological injury in IBD patients, but stricturing CD patients had lower colonic elafin expression than non-stricturing CD patients. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA and protein expression, which may contribute to high circulating elafin levels. Human mesenteric fat adipocytes secrete elafin protein. CONCLUSIONS: High circulating elafin levels are associated with the presence of stricture in CD patients. Serum elafin levels may help identify intestinal strictures in CD patients.


Assuntos
Colite Ulcerativa/sangue , Doença de Crohn/complicações , Elafina/sangue , Obstrução Intestinal/diagnóstico , Gordura Abdominal/citologia , Gordura Abdominal/metabolismo , Adipócitos/metabolismo , Adulto , Estudos de Casos e Controles , Linhagem Celular , Colite Ulcerativa/patologia , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Constrição Patológica/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Elafina/metabolismo , Feminino , Fibroblastos , Voluntários Saudáveis , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Obstrução Intestinal/sangue , Obstrução Intestinal/etiologia , Obstrução Intestinal/patologia , Masculino , Cultura Primária de Células , Estudos Prospectivos , Índice de Gravidade de Doença
12.
Life Sci ; 251: 117609, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32272180

RESUMO

AIMS: To identify the target of an adipose specific aptamer adipo-8, predict the potential interaction between adipo-8 and its target, and investigate lipid-lowering effect of adipo-8 in vitro and in vivo. MAIN METHODS: Distinct membranous protein of 3T3-L1 adipocyte pulled-down by adipo-8 was mass-spectrometry analyzed as target candidate(s), and affinity of adipo-8 to target protein-silent adipocyte was detected to validate it. Interaction between adipo-8 and target was predicted by bioinformatic analysis, further confirmed by aptamer truncation and competitive binding assay. To investigate lipid-lowering effect of adipo-8 and mechanism behind, 250 nmol/L adipo-8 or library was incubated with 3T3-L1 adipocyte or target-protein-silent adipocyte for 24 h, and 0.01 µg/g/day adipo-8 or library was administrated to high-fat-fed male mice for 21 days. KEY FINDINGS: APMAP (Adipocyte Plasma Membrane Associated Protein) was identified as adipo-8 target, and adipo-8 affinity to adipocytes was in proportional to APMAP expression. Docking model between the stem-loop structure of adipo-8 and APMAP were predicted that adipo-8 was likely to interact with APMAP at its amino-acid 275-411 sequence. Moreover, adipo-8 could ameliorate fat deposition through interaction with APMAP in vitro, and administration of adipo-8 in high-fat-diet fed mice resulted in body weight loss and blood triglyceride decrease without liver or renal dysfunction. SIGNIFICANCE: Adipo-8 could recognize APMAP specifically and interact with its targets to ameliorate fat deposition in vitro and in vivo. Aptamer adipo-8 has potential to act as an effective and safe targeted drug for obesity and obesity related diseases.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Glicoproteínas de Membrana/metabolismo , Células 3T3-L1 , Animais , Dieta Hiperlipídica , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular
15.
Clin Sci (Lond) ; 134(8): 1031-1048, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32337536

RESUMO

Global trends in the prevalence of overweight and obesity put the adipocyte in the focus of huge medical interest. This review highlights a new topic in adipose tissue biology, namely the emerging pathogenic role of fat accumulation in bone marrow (BM). Specifically, we summarize current knowledge about the origin and function of BM adipose tissue (BMAT), provide evidence for the association of excess BMAT with diabetes and related cardiovascular complications, and discuss potential therapeutic approaches to correct BMAT dysfunction. There is still a significant uncertainty about the origins and function of BMAT, although several subpopulations of stromal cells have been suggested to have an adipogenic propensity. BM adipocytes are higly plastic and have a distinctive capacity to secrete adipokines that exert local and endocrine functions. BM adiposity is abundant in elderly people and has therefore been interpreted as a component of the whole-body ageing process. BM senescence and BMAT accumulation has been also reported in patients and animal models with Type 2 diabetes, being more pronounced in those with ischaemic complications. Understanding the mechanisms responsible for excess and altered function of BMAT could lead to new treatments able to preserve whole-body homeostasis.


Assuntos
Medula Óssea/metabolismo , Diabetes Mellitus/metabolismo , Gorduras/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus/genética , Humanos
16.
Life Sci ; 248: 117474, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112869

RESUMO

BACKGROUND/OBJECTIVES: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy homeostasis in adipocytes. NNMT expression in adipose tissue is increased in obesity and diabetes. Knockdown of NNMT prevents mice from developing diet-induced obesity, which is closely linked to insulin resistance. An early sign of systemic insulin resistance is reduced expression of glucose transporter 4 (GLUT4) selectively in adipose tissue. Adipose tissue-specific knockout and overexpression of GLUT4 cause reciprocal changes in NNMT expression. The aim of the current study was to elucidate the mechanism that regulates NNMT expression in adipocytes. METHODS: 3T3-L1 adipocytes were cultured in media with varying glucose concentrations or activators and inhibitors of intracellular pathways. NNMT mRNA and protein levels were measured with quantitative polymerase chain reaction and Western blotting. RESULTS: Glucose deprivation of 3T3-L1 adipocytes induced a 2-fold increase in NNMT mRNA and protein expression. This effect was mimicked by inhibition of glucose transport with phloretin, and by inhibition of glycolysis with the phosphoglucose isomerase inhibitor 2-deoxyglucose. Conversely, inhibition of the pentose phosphate pathway did not affect NNMT expression. Pharmacological activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and inhibition of the mammalian target of rapamycin (mTOR) pathway caused an increase in NNMT levels that was similar to the effect of glucose deprivation. Activation of mTOR with MHY1485 prevented the effect of glucose deprivation on NNMT expression. Furthermore, upregulation of NNMT levels depended on functional autophagy and protein translation. CONCLUSION: Glucose availability regulates NNMT expression via an mTOR-dependent mechanism.


Assuntos
Adipócitos/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Glucose/farmacologia , Nicotinamida N-Metiltransferase/genética , Serina-Treonina Quinases TOR/genética , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Transporte Biológico/efeitos dos fármacos , Diferenciação Celular , Desoxiglucose/farmacologia , Metabolismo Energético/genética , Regulação da Expressão Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 4/antagonistas & inibidores , Transportador de Glucose Tipo 4/metabolismo , Glucose-6-Fosfato Isomerase/antagonistas & inibidores , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Homeostase/genética , Camundongos , Morfolinas/farmacologia , Nicotinamida N-Metiltransferase/antagonistas & inibidores , Nicotinamida N-Metiltransferase/metabolismo , Via de Pentose Fosfato/efeitos dos fármacos , Via de Pentose Fosfato/genética , Floretina/farmacologia , Biossíntese de Proteínas , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triazinas/farmacologia
17.
Zhonghua Yi Xue Za Zhi ; 100(6): 456-459, 2020 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-32146770

RESUMO

Objective: To compare the curative effect of mesenchymal stem cells derived from human Wharton's Jelly(WJ-MSC) or adipose(AD-MSC) culture supernatant on endothelial cells angiogenesis. Methods: WJ-MSC and AD-MSC were isolated, identified, and the culture supernatant of stem cells was collected.The WJ-MSC or AD-MSC supernatant co-cultured with the endothelial cells. The expression levels of pro-angiogenic and anti-angiogenic genes of endothelial cells were assessed using qRT-PCR analysis, and the effects of stem cell culture supernatant on angiogenesis were evaluated by performing a tube formation assay in vitro. Results: After adding WJ-MSC and AD-MSC culture supernatant, the expression levels of pro-angiogenic genes in endothelial cells were upregulated, and the expression levels of anti-angiogenic genes were downregulated significantly in both experimental groups compared to the control group (P<0.01), and tube formation of endothelial cells was also significantly increased in both experimental groups as determined by the increase of the tube length ((43.2±9.2) mm vs (94.3±13.2)mm, (86.1±7.2)mm, P<0.01). Conclusion: The results showed that AD-MSC culture supernatant can promote endothelial cells angiogenesis and its curative effect is similar to that of WJ-MSC.


Assuntos
Células-Tronco Mesenquimais , Geleia de Wharton , Adipócitos , Técnicas de Cultura de Células , Diferenciação Celular , Proliferação de Células , Técnicas de Cocultura , Células Endoteliais , Humanos
18.
Life Sci ; 250: 117560, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32198054

RESUMO

AIMS: Dietary calcium a common nutrient of our daily diet found to have an anti-obesity effect which may also regulate insulin sensitivity but this effect and the exact mechanism remains unexplored. Therefore, we aimed to study the effect of different types of calcium diet on insulin sensitivity with respect to the changes in the adipokine secretions in high fat diet (HFD) induced obese rats. MAIN METHODS: Healthy male rats were subjected to HFD for 12 weeks to induce obesity and further exposed to a calcium deficient (0.25% Ca) HFD and calcium enriched (1.0% Ca) HFD for another 12 weeks. Thereafter, all rats were sacrificed to collect the blood, liver, adipose tissue and muscle for downstream analysis. KEY FINDINGS: Calcium enriched HFD (1.0% Ca) significantly reduced (p < 0.01) body weight, adiposity index, glucose level, insulin level, HOMA-IR, adipokines (TNF-α, IL-6, MCP-1, Leptin), hepatic lipid accumulation, hepatic macrophage infiltration, adipocyte hypertrophy and significantly increased (p < 0.01) the adiponectin level, in HFD induced obese rats. The down-regulation of the adipokine secretion significantly increased (p < 0.01) the hepatic and muscle glycogen synthase activity and suppressed the hepatic gluconeogenesis activity via activating the insulin receptor-mediated PI3K/AKT/GLUT insulin signaling pathway thereby improving the insulin sensitivity. On the other hand calcium deficient HFD (0.25% Ca) accelerated the risk of insulin resistance (IR) due to its inability to improve insulin sensitivity by activating the associated pathways. SIGNIFICANCE: Calcium enriched HFD (1.0% Ca) reduced the risk of IR by improving the hepatic and muscle insulin sensitivity by restoring adipokine secretion.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Cálcio na Dieta/administração & dosagem , Resistência à Insulina , Insulina/metabolismo , Obesidade/metabolismo , Adipocinas/sangue , Tecido Adiposo/metabolismo , Animais , Glicemia/análise , Metabolismo dos Carboidratos , Dieta Hiperlipídica , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Músculos/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais
19.
Adv Exp Med Biol ; 1219: 125-142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130697

RESUMO

Obesity has for decades been recognised as one of the major health concerns. Recently accumulated evidence has established that obesity or being overweight is strongly linked to an increased risk of cancer. However, it is still not completely clear how adipose tissue (fat), along with other stromal connective tissues and cells, contribute to tumour initiation and progression. In the tumour microenvironment, the adipose tissue cells, in particular the adipocytes, secrete a number of adipokines, including growth factors, hormones, collagens, fatty acids, and other metabolites as well as extracellular vesicles to shape and condition the tumour and its microenvironment. In fact, the adipocytes, through releasing these factors and materials, can directly and indirectly facilitate cancer cell proliferation, apoptosis, metabolism, angiogenesis, metastasis and even chemotherapy resistance. In this chapter, the multidimensional role played by adipocytes, a major and functional component of the adipose tissue, in promoting cancer development and progression within the tumour microenvironment will be discussed.


Assuntos
Adipócitos/metabolismo , Carcinogênese , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Humanos
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