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1.
Virchows Arch ; 476(1): 29-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31501988

RESUMO

Adipocytic tumors are frequently encountered in routine practice, and while the vast majority represent commonly encountered tumor types (e.g., benign lipoma), the heterogeneity and rarity of other adipocytic neoplasms can pose diagnostic challenges. Atypical and malignant adipocytic tumors account for approximately 20% of all sarcomas. The 2013 World Health Organization (WHO) classification of soft tissue and bone tumors recognizes four major liposarcoma subtypes, characterized by distinct clinical behavior, distinctive morphologies, as well as unique genetic findings: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma. Since the publication of the 2013 WHO classification of soft tissue and bone tumors, the most notable change in the category of adipocytic tumors has been made in the clinicopathologic and molecular characterization of the heterogeneous but distinct group of "atypical low-grade adipocytic neoplasms with spindle cell features," for which the term atypical spindle cell/pleomorphic lipomatous tumor has been proposed. Another substantive change in the group of adipocytic tumors is the introduction of pleomorphic myxoid liposarcoma (myxoid pleomorphic liposarcoma) as an apparently novel subtype of aggressive liposarcoma, especially occurring in children and young adults with a predilection for the mediastinum. This review will further focus upon the diagnostic criteria of these novel emerging entities in the group of adipocytic tumors.


Assuntos
Adipócitos/patologia , Lipoma/patologia , Lipossarcoma/patologia , Humanos , Lipoma/genética , Lipossarcoma/genética , Prognóstico
2.
Anticancer Res ; 39(12): 6653-6660, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810930

RESUMO

AIM: The aim of this study was to investigate the effects of medium-chain triglycerides (MCTs) on chemically-induced hepatic carcinogenesis (HCC) in mice. MATERIALS AND METHODS: In a first set of experiments, mice were treated with diethylnitrosoamine intraperitoneally at two weeks of age. They were fed chow containing MCT or a normal chow diet and sacrificed after 28 weeks. Incidence of hepatic tumor was compared between the two groups. Expression of oxidative stress, and inflammatory cytokines and chemokines in liver tissues were examined. In a second set of experiments, the histopathological findings of the intraperitoneal adipose tissue were assessed, and expression of adipocytokines in the fat tissue was measured. In a third set of experiments, plasma ß-hydroxybutyrate (HB) concentration was measured in both animals fed chow containing MCT and a normal chow diet. Mouse HCC cells were co-cultured with ß-HB, and the numbers of tumor cells were counted at days 3 and 7. RESULTS: In the first set of experiments, the tumor count observed in the control group was significantly blunted in the MCT group. Maximum tumor diameter also decreased in the MCT group compared to the control group. The expression of inflammatory cytokines and chemokines was significantly decreased by MCT. Furthermore, expression of 4-hydroxynonenal was lower in the MCT group compared to the control group. In the second set of experiments, hypertrophy of the adipocytes was suppressed, and the concentration of adiponectin and leptin in the adipose tissue decreased by MCT. In the third set of experiments, plasma ß-HB concentration increased in the MCT group as expected. ß-HB significantly inhibited the proliferation of HCC cells. CONCLUSION: MCT administration markedly suppresses the incidence of chemically-induced HCC by inhibition of inflammation and increase of ketone bodies.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas Experimentais/prevenção & controle , Triglicerídeos/farmacologia , Ácido 3-Hidroxibutírico/sangue , Adipócitos/patologia , Adipocinas/metabolismo , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Aldeídos/metabolismo , Ração Animal/análise , Animais , Carcinógenos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Contagem de Células , Proliferação de Células , Quimiocinas/metabolismo , Citocinas/metabolismo , Dietilnitrosamina , Hipertrofia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leptina/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Estresse Oxidativo , Triglicerídeos/administração & dosagem
5.
Chin J Nat Med ; 17(9): 663-671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31526501

RESUMO

Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids, ellipticine (1) and 9-methoxyellipticine (2), and six known monoterpenoid indole alkaloids (3-8). Lipid-lowering assay in 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC50 = 0.41 and 0.92 µmol·L-1, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 µmol·L-1, being more potent than the positive drug luteolin (EC50 = 2.63 µmol·L-1). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-L1 cells at the early differentiation phase, leading to the retardance of following adipogenesis and lipogenesis. These findings suggest that 1 and 2 may serve as promising leads for further development of anti-obesity drugs.


Assuntos
Adipogenia/efeitos dos fármacos , Carbazóis/farmacologia , Proliferação de Células/efeitos dos fármacos , DNA Super-Helicoidal/química , Hipolipemiantes/farmacologia , Ochrosia/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Carbazóis/química , Carbazóis/metabolismo , Dano ao DNA , Elipticinas/química , Elipticinas/metabolismo , Elipticinas/farmacologia , Hipolipemiantes/química , Hipolipemiantes/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Inibidores da Topoisomerase/química , Inibidores da Topoisomerase/metabolismo , Inibidores da Topoisomerase/farmacologia
6.
Cardiovasc Pathol ; 43: 107144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31491646

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) deposition has a strong association with aspects of metabolic dysfunction, including obesity. The size of the EAT adipocytes in relation to obesity, however, has rarely been researched. Therefore, to contextualise EAT within the broader framework of pathophysiological adipocyte size changes in obesity, we aimed to determine whether EAT adipocyte size is associated with body mass index (BMI). METHODS: During routine post-mortem examination, adipose tissue biopsies were obtained from four depots of 43 cases, including EAT, as well as pericardial (PAT), appendix mesenteric (AAT), and clavicular subcutaneous (SAT) adipose tissues. Tissues were fixed, sectioned, and stained using haematoxylin and eosin. The size (measured as area) of each adipocyte imaged from the depots was analysed in relation to BMI. RESULTS: Mean size of EAT adipocytes was significantly smaller than that from SAT and AAT depots, while not differing from PAT adipocytes. BMI positively correlated with the size of adipocytes isolated from SAT (r=0.5893, P<.0001), PAT (r=0.5854, P<.0001), and AAT (r=0.5829, P<.0001) depots, but not from EAT (r=0.1242, P=.4274), even after multivariate adjustment for age and sex. CONCLUSIONS: EAT adipocyte size is not associated with increased BMI despite significant associations within adipocytes from other adipose depots.


Assuntos
Gordura Abdominal/patologia , Adipócitos/patologia , Adiposidade , Índice de Massa Corporal , Tamanho Celular , Obesidade/patologia , Gordura Subcutânea/patologia , Gordura Abdominal/fisiopatologia , Adulto , Idoso , Autopsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Pericárdio , Estudos Prospectivos , Gordura Subcutânea/fisiopatologia , Adulto Jovem
7.
Eur J Pharmacol ; 861: 172594, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412267

RESUMO

Glucagon like peptide-1 (GLP-1) promotes postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, reduces body weight, improve insulin sensitivity, and alleviate Non Alcoholic Fatty Liver Disease (NAFLD). However, the underlying mechanisms remain unclear. This study aims to explore the underlying mechanisms and cell signaling pathways involved in the anti-obesity and anti-inflammatory effects of liraglutide. Mice were fed a high fat high sucrose diet to induce diabetes, diabetic mice were divided into two groups and injected with liraglutide or vehicle for 14 days. Liraglutide treatment improved insulin sensitivity, accompanied with reduced expression of the phosphorylated Acetyl-CoA carboxylase-2 (ACC2) and upregulation of long chain acyl CoA dehydrogenase (LCAD) in insulin sensitive tissues. Furthermore, liraglutide induced adenosine monophosphate-activated protein kinase-α (AMPK-α) and Sirtuin-1(Sirt-1) protein expression in liver and perigonadal fat. Liraglutide induced elevation of fatty acid oxidation in these tissues may be mediated through the AMPK-Sirt-1 cell signaling pathway. In addition, liraglutide induced brown adipocyte differentiation in skeletal muscle, including induction of uncoupling protein-1 (UCP-1) and PR-domain-containing-16 (PRDM-16) protein in association with induction of SIRT-1. Importantly, liraglutide displayed anti-inflammation effect. Specifically, liraglutide led to a significant reduction in circulating interleukin-1 ß (IL-1 ß) and interleukin-6 (IL-6) as well as hepatic IL-1 ß and IL-6 content. The expression of inducible nitric oxide synthase (iNOS-1) and cyclooxygenase-2 (COX-2) in insulin sensitive tissues was also reduced following liraglutide treatment. In conclusion, liraglutide improves insulin sensitivity through multiple pathways resulting in reduction of inflammation, elevation of fatty acid oxidation, and induction of adaptive thermogenesis.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Liraglutida/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Liraglutida/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
8.
J Physiol Biochem ; 75(3): 391-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31321740

RESUMO

Adipose tissue has long been considered to be involved in tumor progression. However, the adipocyte-secreted molecular determinants that regulate hepatocellular cancer progression have not been defined yet. In this study, the expression pattern of exosome miRNAs in hepatocellular carcinoma (HCC) patients with high body fat ratio (BFR) were identified by using low-density microarray. And the targets of exosome-miRNAs in HCC cells were predicted by bioinformatics methods and verified by in vitro as well as in vivo experiments. Here, we show that microRNA-23a/b (miR-23a/b) was significantly upregulated in both serum exosomes and tumor tissues of HCC patients with a high body fat ratio than low BFR. Subsequently, in vitro studies suggested that miR-23a/b was most likely to be derived from adipocytes and was transported into cancer cells via exosomes, thus promoting HCC cell growth and migration. Meanwhile, exosome miR-23a and miR-23b confer chemoresistance by targeting the von Hippel-Lindau/hypoxia-inducible factor axis. Our study provides evidence in that high BFR-related exosome miR23-a/b is a promising target for future treatment of HCC.


Assuntos
Adipócitos/metabolismo , Carcinoma Hepatocelular/metabolismo , Exossomos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/fisiologia , Obesidade/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Células 3T3-L1 , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Exossomos/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/patologia
9.
Biomed Res Int ; 2019: 3176483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355254

RESUMO

Three lignans, phillyrin, forsythia ester A, and rosin-ß-D-furan glucose, were isolated from Forsythia suspensa which is a famous Traditional Chinese Medicine used for clearing heat and detoxifying, reducing swelling and dispersing knot, and dispersing wind heat. In this study, the effects of phillyrin, forsythia ester A, and rosin-ß-D-furan glucose on insulin resistance of 3T3-L1 adipocytes were investigated by the method of glucose oxidase-peroxidase (GOD-POD) and the mechanism was assayed by the method of western blot. The results indicated that phillyrin, forsythia ester A, and rosin-ß-D-furan glucose could improve the glucose uptake in 3T3-L1 adipocytes under insulin resistance (IR). Among them, phillyrin showed significant activity in increasing glucose consumption at the concentrations of 100 µM and 200 µM (P < 0.001). The mechanism of improving insulin resistance may be that phillyrin could raise the protein phosphorylation of IRS-1 and Akt and the expression levels of GLUT4 protein.


Assuntos
Adipócitos/metabolismo , Forsythia/química , Glucosídeos , Resistência à Insulina , Folhas de Planta/química , Células 3T3-L1 , Adipócitos/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/biossíntese , Glucosídeos/química , Glucosídeos/farmacologia , Proteínas Substratos do Receptor de Insulina/biossíntese , Camundongos , Proteínas Proto-Oncogênicas c-akt/biossíntese
10.
Nutrients ; 11(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234305

RESUMO

Bone is a complex tissue composing of mineralized bone, bone cells, hematopoietic cells, marrow adipocytes, and supportive stromal cells. The homeostasis of bone and marrow niche is dynamically regulated by nutrients. The positive correlation between cardiovascular disease and osteoporosis risk suggests a close relationship between hyperlipidemia and/or hypercholesterolemia and the bone metabolism. Cholesterol and its metabolites influence the bone homeostasis through modulating the differentiation and activation of osteoblasts and osteoclasts. The effects of cholesterol on hematopoietic stem cells, including proliferation, migration, and differentiation, are also well-documented and further relate to atherosclerotic lesions. Correlation between circulating cholesterol and bone marrow adipocytes remains elusive, which seems opposite to its effects on osteoblasts. Epidemiological evidence has demonstrated that cholesterol deteriorates or benefits bone metabolism depending on the types, such as low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol. In this review, we will summarize the latest progress of how cholesterol regulates bone metabolism and bone marrow microenvironment, including the hematopoiesis and marrow adiposity. Elucidation of these association and factors is of great importance in developing therapeutic options for bone related diseases under hypercholesterolemic conditions.


Assuntos
Células da Medula Óssea/metabolismo , Osso e Ossos/metabolismo , Microambiente Celular , Colesterol/sangue , Hipercolesterolemia/sangue , Adipócitos/metabolismo , Adipócitos/patologia , Adiposidade , Animais , Células da Medula Óssea/patologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Movimento Celular , Proliferação de Células , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Hipercolesterolemia/patologia , Hipercolesterolemia/fisiopatologia , Fenótipo , Transdução de Sinais , Nicho de Células-Tronco
11.
Gene ; 710: 406-414, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31200087

RESUMO

Integrins are cell attachment receptors that function in the communication between the intracellular and extracellular compartments. Integrins and extra cellular matrix (ECM) collaborate to regulate gene expression by extracellular signal-regulated kinases (ERKs). Integrins as regulators, have critical role in ECM remodeling. Fibrosis is the hallmark of obesity and insulin resistance originated by aberrant ECM remodeling. Therefore deciphering integrins' expression profile in cells at different conditions is worthy. The aim of this study is evaluation of integrins' gene expression profile changes in mouse 3T3-L1 preadipocytes, adipocytes, insulin resistant and hypertrophic adipocytes. For this purpose, we differentiated mouse 3T3-L1 preadipocytes to adipocytes, insulin resistant and hypertrophied adipocytes and assayed integrins' gene expression in four conditions by real time-PCR. Also the proteins expression changes of ERK and collagen VI assayed by Western blotting. Data analysis has shown that integrins' gene expression changes throughout adipocyte differentiation and pathological processes. The expressions of many integrins genes were significantly up- or down-regulated by >1.5-fold during differentiation, insulin resistant, and hypertrophic adipocytes. In addition to changes in the type of integrin, the integrins expression levels were different. Integrins, on the whole were more expressed in pathological processes relative to normal adipocytes. Also, phosphorylation of ERK 1,2 was increased >1.5-fold in differentiated, insulin resistant and hypertrophied adipocytes versus preadipocytes. Collagen VI only increased 2-fold in hypertrophied adipocytes. Examination of the total integrin gene family expression during adipocyte differentiation and pathological processes, leads to the identification of differential integrin gene expression. These results suggest that the type of integrin may not only play a role in adipocyte differentiation but also in pathological processes which may associate to increased ERK pathway activity in these conditions.


Assuntos
Adipócitos/citologia , Adipócitos/patologia , Perfilação da Expressão Gênica/métodos , Integrinas/genética , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Diferenciação Celular , Colágeno Tipo VII/metabolismo , Regulação da Expressão Gênica , Hipertrofia , Resistência à Insulina , Sistema de Sinalização das MAP Quinases , Camundongos , Família Multigênica , Fosforilação
12.
Nat Commun ; 10(1): 2430, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160583

RESUMO

Muscle loss due to fibrotic or adipogenic replacement of myofibers is common in muscle diseases and muscle-resident fibro/adipogenic precursors (FAPs) are implicated in this process. While FAP-mediated muscle fibrosis is widely studied in muscle diseases, the role of FAPs in adipogenic muscle loss is not well understood. Adipogenic muscle loss is a feature of limb girdle muscular dystrophy 2B (LGMD2B) - a disease caused by mutations in dysferlin. Here we show that FAPs cause the adipogenic loss of dysferlin deficient muscle. Progressive accumulation of Annexin A2 (AnxA2) in the myofiber matrix causes FAP differentiation into adipocytes. Lack of AnxA2 prevents FAP adipogenesis, protecting against adipogenic loss of dysferlinopathic muscle while exogenous AnxA2 enhances muscle loss. Pharmacological inhibition of FAP adipogenesis arrests adipogenic replacement and degeneration of dysferlin-deficient muscle. These results demonstrate the pathogenic role of FAPs in LGMD2B and establish these cells as therapeutic targets to ameliorate muscle loss in patients.


Assuntos
Tecido Adiposo/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Células-Tronco/citologia , Adipócitos/patologia , Adipogenia/efeitos dos fármacos , Tecido Adiposo/patologia , Adolescente , Idade de Início , Animais , Anexina A2/metabolismo , Estudos de Casos e Controles , Disferlina/genética , Venenos Elapídicos/toxicidade , Feminino , Fibrose , Humanos , Técnicas In Vitro , Masculino , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia , Inibidores de Proteases/farmacologia , Índice de Gravidade de Doença , Células-Tronco/efeitos dos fármacos , Tiofenos/farmacologia , Adulto Jovem
13.
Nat Commun ; 10(1): 2375, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147543

RESUMO

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. Obesity, as a worldwide healthcare problem, has attracted more and more attention. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL). HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.


Assuntos
Tecido Adiposo Branco/metabolismo , Proteína Semelhante a ELAV 1/genética , Intolerância à Glucose/genética , Hipercolesterolemia/genética , Resistência à Insulina/genética , Lipase/genética , Obesidade/genética , Adipócitos/patologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/imunologia , Animais , Crescimento Celular , Dieta Hiperlipídica , Proteína Semelhante a ELAV 1/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Intolerância à Glucose/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hipertrofia , Inflamação/imunologia , Lipase/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Biossíntese de Proteínas , Estabilidade de RNA/genética , Gordura Subcutânea/metabolismo
14.
J Cutan Pathol ; 46(10): 778-783, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31115930

RESUMO

The low-fat and fat-free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the diagnosis relies on its non-lipogenic component analysis. Here, we report the clinicopathological features of two oral SCLs (low-fat and fat-free variants). Both lesions presented clinically as an asymptomatic nodule, which initially yielded diagnostic difficulties on the morphological analysis alone. One case was diagnosed as low-fat SCL on the lower lip in a 29-year-old man, and the other as fat-free SCL on the buccal mucosa in a 46-year-old man. In both cases, immunohistochemistry showed strong positivity for CD34 and, remarkably, retinoblastoma (Rb) protein was deficient. Mast cell (MC) tryptase and toluidine blue stain highlighted numerous MCs distributed throughout all tumor stroma. Alpha-SMA and desmin were negative. S100 evidenced scarce adipocytes only in the low-fat SCL case. Conservative surgical treatment was performed and no recurrence was noticed in about 2-year of follow-up in both cases. Because of the potential pitfalls, careful morphological analysis of the tumor stroma in the low-fat/fat-free SCL diagnosis, supported by immunohistochemistry (especially CD34, Rb and MC tryptase), is strongly recommended. To the best of our knowledge, these are the first and second cases reported of fat-free and low-fat SCL in the oral cavity.


Assuntos
Adipócitos , Lipoma , Neoplasias Bucais , Sarcoma , Adipócitos/metabolismo , Adipócitos/patologia , Adulto , Humanos , Lipoma/metabolismo , Lipoma/patologia , Masculino , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Sarcoma/metabolismo , Sarcoma/patologia
15.
Mol Med Rep ; 19(6): 4719-4726, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059010

RESUMO

Leukemia inhibitory factor (LIF) modulates various biological processes. Although previous studies have described the effects of LIF on adipocyte differentiation, the role of LIF receptor (LIFR) on adipocyte differentiation remains unclear. Using reverse transcription­quantitative PCR (RT­qPCR), LIFR expression was demonstrated to increase during adipogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs), indicating that LIFR may be involved in this process. To further evaluate the association between LIFR and adipogenic differentiation, lentivirus­mediated LIFR knockdown was performed in hMSCs. Cells were divided into two groups: Negative control group and LIFR­knockdown group. During the adipogenic differentiation process, intracellular lipid accumulation was assessed with Oil Red O staining at various time points (days 3, 6 and 9). Additionally, the mRNA and protein expression levels of LIF, LIFR and three molecular indicators of adipogenesis, peroxisome proliferator­activated receptor Î³ (PPARγ), CCAAT enhancer binding protein α (C/EBPα) and fatty acid binding protein 4 (FABP4/aP2), were assessed by RT­qPCR and western blotting. The culture supernatant was collected to evaluate the concentration of LIF using ELISA. The present results suggested that LIFR expression progressively increased during adipogenic differentiation of hMSCs. Conversely, LIFR knockdown significantly suppressed this process. Additionally, PPARγ, C/EBPα and aP2 were inhibited following LIFR knockdown. In contrast with LIFR, the expression levels of LIF were significantly decreased after the initiation of adipogenic differentiation. Therefore, the expression levels of LIF and LIFR exhibited opposite trends. Collectively, the present results suggested that LIFR promoted adipogenic differentiation, whereas LIF may negatively regulate this process.


Assuntos
Adipogenia/fisiologia , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Células-Tronco Mesenquimais/fisiologia , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/genética , Células da Medula Óssea , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/genética , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Células-Tronco Mesenquimais/patologia , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/metabolismo
16.
Nutrients ; 11(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137609

RESUMO

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/prevenção & controle , Oryza , Extratos Vegetais/farmacologia , Sementes , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/genética , Animais , Fármacos Antiobesidade/isolamento & purificação , Modelos Animais de Doenças , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Obesidade/sangue , Obesidade/patologia , Obesidade/fisiopatologia , Oryza/química , Fosforilação , Extratos Vegetais/isolamento & purificação , Sementes/química , Transdução de Sinais , Ganho de Peso/efeitos dos fármacos
17.
Reprod Biol Endocrinol ; 17(1): 36, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30982470

RESUMO

BACKGROUND: Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5-10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. METHODS: Primary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis. RESULTS: Gene expression analysis showed that endometriosis altered the expression of Cebpa, Cebpb, Ppar-γ, leptin, adiponectin, IL-6, and HSL, which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells. CONCLUSIONS: We demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.


Assuntos
Adipócitos/patologia , Endometriose/patologia , Adipócitos/metabolismo , Animais , Diferenciação Celular/genética , Proliferação de Células , Endometriose/genética , Endometriose/metabolismo , Feminino , Expressão Gênica , Humanos , Resistência à Insulina/genética , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo
18.
Cell Physiol Biochem ; 52(5): 1151-1165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30990585

RESUMO

BACKGROUND/AIMS: Adipocyte hypertrophy in obesity is associated with inflammation and adipose tissue fibrosis which both contribute to metabolic diseases. Mechanisms regulating lipid droplet expansion are poorly understood. Knock down of the scaffold protein beta 2 syntrophin (SNTB2) increases lipid droplet size of 3T3-L1 adipocytes and the physiological relevance of SNTB2 in adipose tissue morphology and metabolic health was analyzed herein. METHODS: Wild type and SNTB2-/- mice were challenged with 24 weeks high fat diet. Adipose tissue morphology and expression of various genes / proteins including collagens and caveolin-1 was examined. Glucose, insulin, fasting and fed free fatty acids were measured in serum. SNTB2 expression was determined in adipose tissues of patients. RESULTS: Upon high fat diet SNTB2-/- mice displayed reduced adiposity and adipocyte hypertrophy. Expression of various proteins was normal in the different white fat depots of SNTB2-/- mice while caveolin-1 protein and collagen mRNA levels were diminished. Null mice had reduced systemic glucose while fasting and postprandial insulin and insulin response were normal. Fatty acid clearance in the fed state and after insulin injection was enhanced. SNTB2 and caveolin-1 were increased in fat of ob/ob mice. However, no correlation between body mass index and SNTB2 protein in adipose tissues of seven patients was found. In subcutaneous but not in visceral fat the ratio of SNTB2 to alpha syntrophin protein, which affects lipid droplet size in the opposite manner, was associated with BMI. In subcutaneous fat of extremely obese patients SNTB2 mRNA levels were not correlated with weight loss after bariatric surgery. CONCLUSION: Current study shows that high SNTB2 in obese adipose tissues restricts adipocyte growth and thereby may contribute to metabolic diseases.


Assuntos
Adipócitos/metabolismo , Gorduras na Dieta/farmacologia , Proteínas Associadas à Distrofina , Metabolismo dos Lipídeos , Obesidade/metabolismo , Período Pós-Prandial , Adipócitos/patologia , Adulto , Idoso , Animais , Caveolina 1/genética , Caveolina 1/metabolismo , Proteínas Associadas à Distrofina/genética , Proteínas Associadas à Distrofina/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia
19.
Mol Nutr Food Res ; 63(10): e1801413, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31018035

RESUMO

SCOPE: The aim is to assess the action of an aqueous extract from cocoa shell (CAE) and its main phenolic compounds to prevent the loss of obesity-induced mitochondrial function and insulin sensitivity, targeting inflammation between macrophages-adipocytes in vitro. METHODS AND RESULTS: CAE (31-500 µg mL-1 ) inhibits 3T3-L1 adipocytes lipid accumulation and induces browning during differentiation. LPS-stimulated RAW264.7 macrophages show reduced inducible nitric oxide synthase and cyclooxygenase-2 expression and lowered pro-inflammatory cytokine production when treated with CAE and pure phenolics. Inflammatory crosstalk created by stimulating adipocytes with macrophage-conditioned media (CM) is arrested; CAE diminishes tumor necrosis factor-α (67%) and promotes adiponectin secretion (12.3-fold). Mitochondrial function, measured by reactive oxygen species production, mitochondrial content, and activity, is preserved in CM-treated adipocytes through up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-α expression. Increases in insulin receptor (9-fold), phosphoinositide 3-kinase (3-fold), protein kinase B (4-fold) phosphorylation, and a decrease in insulin receptor substrate 1 serine phosphorylation induce increased glucose uptake (34%) and glucose transporter 4 translocation (14-fold) in CM-induced adipocytes. CONCLUSION: CAE phenolics promote a beige phenotype in adipocytes. Macrophages-adipocytes inflammatory interaction is reduced preventing mitochondrial dysfunction and insulin resistance. For the first time, CAE shows a positive effect on adipogenesis and inflammation-related disorders.


Assuntos
Adipócitos/efeitos dos fármacos , Cacau/química , Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Biflavonoides/farmacologia , Catequina/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Hidroxibenzoatos/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Mitocôndrias/metabolismo , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Proantocianidinas/farmacologia , Células RAW 264.7
20.
ACS Appl Mater Interfaces ; 11(16): 14548-14559, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30943004

RESUMO

Osteosarcoma is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. Unfolding of effectual therapeutic strategies against osteosarcoma is impeded because of the absence of adequate animal models, which can truly recapitulate disease biology of humans. Tissue engineering provides an opportunity to develop physiologically relevant, reproducible, and tunable in vitro platforms to investigate the interactions of osteosarcoma cells with its microenvironment. Adipose-derived stem cells (ASCs) are detected adjacent to osteosarcoma masses and are considered to have protumor effects. Hence, the present study focuses on investigating the role of reactive ASCs in formation of spheroids of osteosarcoma cells (Saos 2) within a three-dimensional (3D) niche, which is created using gellan gum (GG)-silk fibroin. By modifying the blending ratio of GG-silk, the optimum stiffness of the resultant hydrogels such as GG and GG75: S25 is obtained for cancer spheroid formation. This work indicates that the co-existence of cancer and stem cells can form a spheroid, the hallmark of cancer, only in particular microenvironment stiffness. The incorporation of fibrillar silk fibroin within the hydrophilic network of GG in GG75: S25 spongy-like hydrogels closely mimics the stiffness of commercially established cancer biomaterials (e.g., Matrigel, HyStem). The GG75: S25 hydrogel maintains the metabolically active construct for a longer time with elevated expression of osteopontin, osteocalcin, RUNX 2, and bone sialoprotein genes, the biomarkers of osteosarcoma, compared to GG. The GG75: S25 construct also exhibits intense alkaline phosphatase expression in immunohistochemistry compared to GG, indicating itspotentiality to serve as biomimetic niche to model osteosarcoma. Taken together, the GG-silk fibroin-blended spongy-like hydrogel is envisioned as an alternative low-cost platform for 3D cancer modeling.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Neoplasias Ósseas/metabolismo , Fibroínas/química , Hidrogéis/química , Modelos Biológicos , Osteossarcoma/metabolismo , Esferoides Celulares/metabolismo , Células-Tronco/metabolismo , Tecidos Suporte/química , Adipócitos/patologia , Tecido Adiposo/patologia , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Humanos , Osteossarcoma/patologia , Esferoides Celulares/patologia , Células-Tronco/patologia , Engenharia Tecidual
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