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1.
Life Sci ; 265: 118790, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33220294

RESUMO

Epidemiologic evidence suggests that obesity and sedentary are modifiable factors strongly associated with breast cancer risk worldwide. Since breast cancer represents the most frequent malignant neoplasm and the second cause of cancer-related deaths in women worldwide, an insight into the molecular mechanisms clarifying the effects of physical activity in breast cancer cells could have important implication for changing this cancer burden. In this narrative Review article, we summarize the current knowledge, regarding the effects of adapted physical activity program, focusing on the cellular signaling pathways activated and on the molecular markers involved in breast cancer. Regular exercise training in breast cancer patients has been shown to positively affect tumor-growth and survival rate. Indeed, emerging work demonstrates that regular exercise is able to affect multiple cancer hallmarks influencing the development and progression of cancer. In conclusion, changes in the circulating insulin, adipokines and estrogen levels, inflammation and oxidative stress could represent some of the possible biological mechanisms through which exercise may influence breast cancer development and recurrence.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Exercício Físico/fisiologia , Transdução de Sinais/fisiologia , Adipocinas/metabolismo , Animais , Neoplasias da Mama/terapia , Estrogênios/metabolismo , Feminino , Humanos , Insulina/metabolismo , Microambiente Tumoral/fisiologia
2.
Medicine (Baltimore) ; 99(50): e22964, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327229

RESUMO

Long non-coding RNAs (lncRNAs) have been evidenced to be associated with the development of multiple diseases. However, the expression pattern and function of lncRNAs in acute ischemic stroke remain unclear. To determine the differential expression of lncRNAs in acute ischemic stroke, we analyzed the expression profile of lncRNAs by high-throughput sequencing analysis. Gene Ontology (GO) and pathway analyses were employed to analyze the gene function and identify enriched pathways of the differentially expressed lncRNAs. We also built an lncRNA-mRNA expression correlation network and verified the interactions of selected lncRNAs in acute ischemic stroke. To further confirm the results of the expression profile, 6 differentially expressed lncRNAs were randomly selected and quantitative RT-PCR (qRT-PCR) performed. We identified 44,578 aberrantly expressed lncRNAs, including 228 upregulated and 16 downregulated lncRNAs. The qRT-PCR results showed that ENSG00000269900, ENSG00000196559, ENSG00000202198, ENSG00000226482, ENSG00000260539 (up), and XLOC_013994_2 (down) were abnormally expressed, which was consistent with the sequencing results. The upregulated expression of lncRNA ENSG00000226482 may activate the adipocytokine signaling pathway, resulting in acute ischemia stroke. In summary, we analyzed the lncRNAs expression profile in acute ischemic stroke patients and identified the functions and enriched metabolic pathways, proposing new insights into the diagnostic and therapeutic biomarkers for this disease.


Assuntos
Biomarcadores/metabolismo , RNA Longo não Codificante/genética , Adipocinas/metabolismo , Idoso , Estudos de Casos e Controles , China/epidemiologia , Regulação para Baixo , Feminino , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Tomografia Computadorizada por Raios X/métodos , Regulação para Cima
3.
Niger J Clin Pract ; 23(10): 1345-1355, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33047690

RESUMO

Background: Several studies have demonstrated an association between obesity, periodontitis, and exercise. Aims: This study aimed to investigate the effects of regular exercise on obese women with periodontal disease, using serum, saliva, and gingival crevicular fluid (GCF) samples. A before-after study design was adopted to evaluate the effects of 12 weeks of regular exercise on obese women grouped according to periodontal status, without a control group (no exercise). The study sample comprised of 15 patients without periodontitis (NP group) and 10 patients with chronic periodontitis (CP group), from whom periodontal parameters were measured and serum, saliva, and GCF samples were collected. Body mass index (BMI), anthropometric measurements, somatotype-motoric tests, and maximal oxygen consumption (VO2max) were recorded at baseline and after exercise. Subjects and Methods: Med Calc was used for statistical analysis. Results: After exercise, a significant decrease in BMI and a significant increase in VO2max were observed in both groups. A significant decrease in probing depth and clinical attachment loss, serum leptin, GCF tumor necrosis factor-α(TNF-α) and leptin, and a significant increase in GCF resistin were observed in the CP group. A significant decrease in serum TNF-α and leptin levels and a significant increase in serum resistin and GCF TNF-α, leptin, resistin, and adiponectin levels were observed in the NP group. Significant correlations between bleeding on probing and levels of interleukin-1ß and leptin in GCF were observed in the CP group. Conclusions: This study showed that regular exercise exerts different impacts with respect to clinical and biochemical aspects of periodontal and systemic conditions in obese women.


Assuntos
Adipocinas/metabolismo , Periodontite Crônica/complicações , Periodontite Crônica/metabolismo , Exercício Físico/fisiologia , Líquido do Sulco Gengival/química , Obesidade/complicações , Saliva/química , Adipocinas/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Periodontite Crônica/sangue , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Bolsa Periodontal/metabolismo , Resistina/sangue , Resistina/metabolismo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
4.
PLoS One ; 15(10): e0239130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33006980

RESUMO

OBJECTIVE: Examine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes. METHODS: Fourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences. RESULTS: SC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01). CONCLUSION: Adding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism.


Assuntos
Cirurgia Bariátrica , Terapia por Exercício/métodos , Exercício Físico , Obesidade Mórbida/cirurgia , Obesidade Mórbida/terapia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Adulto , Composição Corporal , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/metabolismo , Aptidão Física , Projetos Piloto , Cuidados Pré-Operatórios/métodos , Período Pré-Operatório , Resultado do Tratamento
5.
Arterioscler Thromb Vasc Biol ; 40(11): 2569-2576, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32878476

RESUMO

Atherosclerosis is orchestrated by complex interactions between vascular and inflammatory cells. Traditionally, it has been considered to be an intimal inflammatory disease, characterized by endothelial dysfunction, inflammatory cell recruitment, lipid oxidation, and foam cell formation. This inside-out signaling paradigm has been accepted as dogma for many years, despite the fact that inflammatory cells are far more prevalent in the adventitia compared with the intima. For decades, the origin of adventitial inflammation in atherosclerosis was unknown. The fact that these inflammatory cells were observed to cluster at the margin of perivascular adipose tissues-a unique and highly inflammatory adipose depot that surrounds most atherosclerosis-prone blood vessels-has stimulated interest in perivascular adipose tissue-mediated outside-in signaling in vascular pathophysiology, including atherosclerosis. The phenotype of perivascular adipocytes underlies the functional characteristics of this depot, including its role in adventitial inflammatory cell recruitment, trafficking to the intima via the vasa vasorum, and atherosclerosis perturbation. This review is focused on emerging concepts pertaining to outside-in signaling in atherosclerosis driven by dysfunctional perivascular adipose tissues during diet-induced obesity and recent strategies for atherosclerosis prediction and prognostication based upon this hypothesis.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Aterosclerose/metabolismo , Vasos Sanguíneos/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Animais , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Comunicação Celular , Humanos , Inflamação/patologia , Inflamação/fisiopatologia , Placa Aterosclerótica , Transdução de Sinais
6.
PLoS One ; 15(9): e0238638, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966299

RESUMO

Obesity is characterized by a low degree of chronic inflammation state that, along with metabolic modifications, promotes important changes in the animal's organism. Adipose tissue actively participates in inflammation and immunity, and several defense cells of the organism may, therefore, be involved in the diversity found between obese and ideal weight individuals. Studies regarding this subject have shown immune cell changes in humans and rats, however, the literature is scarce in relation to dogs. Thus, the present study aimed to evaluate the gene expression profile of immunoinflammatory response and the lymphoproliferation of obese dogs before and after weight loss. Eight female dogs, neutered, of different breeds, aged between 1 and 8 years (4.74±3.19), obese, with body condition score (BCS) of 9 out of a 9-point scale and body composition determined by the deuterium isotope dilution method were included. The obese dogs were enrolled in a weight loss program and after losing 20% of their initial weight became a second experimental group. A third experimental group consisted of eight female dogs, neutered, aged between 1 and 8 years (3.11±0.78) and with ideal BCS (5 out of a 9-point scale). Gene expression of immunoinflammatory cytokines (resistin, leptin, adiponectin, TNF-α, IL-6, IL-8, and IL-10) was assessed by qRT-PCR and immunity was assessed by lymphoproliferative response using the flow cytometry technique. The data that presented normal distribution was evaluated by analysis of variance by the PROC MIXED of the SAS and when differences were detected, these were compared by the Tukey test. Regarding the gene expression data, the procedure PROC GLIMMIX was adopted and the methodology of generalized linear model was used, in which the Gama distribution proved to be adequate. Values of p<0.05 were considered significant. The mean weight loss period of the animals included in the study was 194.25 ± 28.31 days and the mean weekly weight loss rate was 1.02 ± 0.82%. The average fat mass, both in percentage (P<0.001) and in kilograms (P = 0.012), was higher in the obese group (40.88%; 8.91kg), returning to normal and without difference between the control group (19.16%; 3.01kg) and after weight loss (22.10%; 4.11kg). The weight loss program resulted in an increase in percentage of lean body mass (P = 0.001), 55.50% in obese animals vs 77.90% in obese dogs after weight loss, the latter with no difference when compared to the control group (80.84%). The obese group presented increased gene expression of resistin and IL-8 in relation to the weight loss group (P = 0.002). In adiponectin, the obese group presented increased mRNA gene expression when compared to the weight loss group (P = 0.003). The evaluation of lymphocyte proliferation showed differences between the group of obese animals before and after weight loss (P = 0.004). Weight loss resulted in an increase in the lymphoproliferation rate (18.48%) compared to obese dogs at the beginning of the study (10.71%). These results indicate that weight loss modulates the immunoinflammatory response of obese dogs and may present important benefits to health and longevity of dogs.


Assuntos
Cães/genética , Cães/imunologia , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/imunologia , Obesidade/genética , Obesidade/imunologia , Perda de Peso/genética , Adipocinas/genética , Adipocinas/metabolismo , Animais , Feminino , Linfócitos/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
J Steroid Biochem Mol Biol ; 203: 105737, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32818561

RESUMO

Abdominal obesity may be defined as excess deposits of fat in the abdominal region. It is a common health condition seen in South Asians and is positively related to non-communicable diseases (NCDs). It is independent of body mass index and measured by raised waist circumference for men≥90 cm and women≥80 cm. The reason for its prevalence being common in Indians finds its root from pregnancy, during fetal period and has emerged as a concept of 'Thin Fat Indian'. Malnutrition in such a critical period of growth has consequences in the form of reduced basal metabolic rate (BMR), reduced blood flow to growing tissues, reduced functional ability of vital organs, endocrine changes and reduced capacity of primary adipose tissue. However, excess of visceral fat facilitates high dosage of adipokines in the portal vein to liver and other body tissues having serious implications seen in the form NCDs like diabetes, hypertension, heart diseases, non-alcoholic fatty liver diseases, kidney disorders, cancer and other health problems. Abdominal obesity should be addressed before it has progressed further to defined health issues by exercise and diet, so that people can live a quality life.


Assuntos
Doenças não Transmissíveis/epidemiologia , Obesidade Abdominal/epidemiologia , Adipocinas/metabolismo , Grupo com Ancestrais do Continente Asiático , Índice de Massa Corporal , Grupo com Ancestrais do Continente Europeu , Humanos , Doenças não Transmissíveis/etnologia , Obesidade Abdominal/etnologia , Grupo com Ancestrais Oceânicos
8.
Oncogene ; 39(38): 6071-6084, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32796958

RESUMO

The long non-coding RNA (LncRNA) abnormally expresses in several cancers including non-small cell lung cancer (NSCLC). To better understand the role of key lncRNA involving cancer progress, we conduct a comprehensive data mining on LINC00467 and determine its molecular mechanisms. We identified LINC00467 was the up-regulated lncRNA that common significantly differentially expressed in NSCLC and CRC tissues from GEO database. LINC00467 highly expressed in NSCLC tissues and associated with advanced clinical stages and poor outcome. Knockdown of LINC00467 inhibited cell growth and metastasis via regulating the Akt signaling pathway. Finally, we demonstrated that TDG mediated acetylation is the key factor controlling LINC00467 expression. In conclusion, LINC00467 promotes NSCLC progression via Akt signal pathway. The identified LINC00467 may serve as a valuable diagnostic and prognostic biomarker as well as a therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/genética , Acetilação , Adipocinas/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Progressão da Doença , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Camundongos , Modelos Biológicos , Metástase Neoplásica , Estadiamento de Neoplasias , Ligação Proteica , Proteólise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Transdução de Sinais
9.
Cardiovasc Pathol ; 49: 107259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692664

RESUMO

Perivascular adipose tissue (PVAT) is a fat tissue deposit that encircles the vasculature. PVAT is traditionally known to protect the vasculature from external stimuli that could cause biological stress. In addition to the protective role of PVAT, it secretes certain biologically active substances known as adipokines that induce paracrine effects on proximate blood vessels. These adipokines influence vascular tones. There are different types of PVAT and they are phenotypically and functionally distinct. These are the white and brown PVATs. Under certain conditions, white PVAT could undergo phenotypic switch to attain a brown PVAT-like phenotype. This type of PVAT is referred to as Beige PVAT. The morphology of adipose tissue is influenced by species, age, and sex. These factors play significant roles in adipose tissue mass, functionality, paracrine activity, and predisposition to vascular diseases. The difficulty that is currently experienced in extrapolating animal models to human physiology could be traceable to these factors. Up till now, the involvement of PVAT in the development of vascular pathology is still not well understood. Brown and white PVAT contribute differently to vascular pathology. Thus, the PVAT could be a therapeutic target in curbing certain vascular diseases. In this review, knowledge would be updated on the multifaceted involvement of PVAT in vascular pathology and also explore its vascular therapeutic potential.


Assuntos
Tecido Adiposo Bege/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Artérias/patologia , Doenças Vasculares/patologia , Adipocinas/metabolismo , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Bege/fisiopatologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Adiposidade , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Artérias/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Hemodinâmica , Humanos , Mediadores da Inflamação/metabolismo , Comunicação Parácrina , Transdução de Sinais , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologia
10.
Proc Natl Acad Sci U S A ; 117(29): 17381-17388, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632018

RESUMO

Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.


Assuntos
Adiponectina/metabolismo , Complemento C1q/metabolismo , Fosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adipocinas/metabolismo , Adiponectina/genética , Animais , Ânions , Membrana Celular , LDL-Colesterol , Humanos , Metabolismo dos Lipídeos , Lipidômica , Lipoproteínas/metabolismo , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Opsonizantes/metabolismo , Plasma
11.
Gen Physiol Biophys ; 39(3): 239-248, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32525817

RESUMO

Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor. Obesity has been confirmed to be closely related to the occurrence of CRC, but the specific mechanism is not clear. This study mainly explored the roles of obesity-related genes, fatty acid synthase (FASN) and zinc-alpha-2-glycoprotein (AZGP1), in CRC. 30 cases of CRC tissues and adjacent normal colorectal tissues were obtained to quantify the levels of FASN and AZGP1 using qRT-PCR and Western blotting. Overexpression-AZGP1, overexpression-FASN and FASN shRNA were transfected into SW480 cells. CCK-8, wound healing and Transwell assays were used to evaluate the roles of FASN and AZGP1 on cell proliferation, migration as well as invasion. Western blot was performed to investigate the expression of MMP-2, MMP-9 and mTOR signaling-related proteins. AZGP1 expression was decreased in CRC tissues, which was negatively correlated with FASN expression. Overexpression-AZGP1 showed a significant inhibitory effect on cell proliferation, invasion and migration via inhibiting MMP-2 and MMP-9 expressions. Furthermore, up-regulation of AZGP1 suppressed the expression of mTOR pathway downstream proteins 4EBP and eIF4E through inhibiting FASN expression. Reintroduction of overexpression-FASN could partially reverse and inhibition of FASN further decrease the anti-tumor effect of AZGP1. AZGP1 suppresses CRC cellular activities by regulating FASN via mTOR pathway, suggesting that AZGP1 and FASN may be the targets for CRC therapy.


Assuntos
Adipocinas/metabolismo , Neoplasias Colorretais/patologia , Ácido Graxo Sintase Tipo I/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica
12.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165858, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531260

RESUMO

As the population ages, obesity and metabolic complications as well as neurological disorders are becoming more prevalent, with huge economic burdens on both societies and families. New therapeutics are urgently needed. Nerve growth factor (NGF), first discovered in 1950s, is a neurotrophic factor involved in regulating cell proliferation, growth, survival, and apoptosis in both central and peripheral nervous systems. NGF and its precursor, proNGF, bind to TrkA and p75 receptors and initiate protein phosphorylation cascades, resulting in changes of cellular functions, and are associated with obesity, diabetes and its complications, and Alzheimer's disease. In this article, we summarize changes in NGF levels in metabolic and neuronal disorders, the signal transduction initiated by NGF and proNGF, the physiological and pathophysiological relevance, and therapeutic potential in treating chronic metabolic diseases and cognitive decline.


Assuntos
Doença de Alzheimer/patologia , Neuropatias Diabéticas/patologia , Retinopatia Diabética/patologia , Fator de Crescimento Neural/metabolismo , Obesidade/complicações , Precursores de Proteínas/metabolismo , Adipocinas/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cognição/efeitos dos fármacos , Cognição/fisiologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/terapia , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/terapia , Modelos Animais de Doenças , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Camundongos , Fator de Crescimento Neural/administração & dosagem , Fator de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Células-Tronco Neurais/transplante , Obesidade/metabolismo , Obesidade/patologia , Obesidade/terapia , Soluções Oftálmicas/administração & dosagem , Parvovirinae/genética , Precursores de Proteínas/administração & dosagem , Ratos , Receptor trkA/metabolismo , Transdução de Sinais
13.
Microvasc Res ; 131: 104023, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32485192

RESUMO

INTRODUCTION: Obesity is a chronic disease responsible for a high morbidity and mortality rate, with an increasing worldwide prevalence. Obesity is associated with immune responses characterized by chronic systemic inflammation. This article focuses on the mechanisms that explain the proposed link between obesity-associated diseases and inflammation. Also, it describes the role of inflammatory molecules in obesity-associated metabolic abnormalities. METHODS: More than 200 articles were selected and consulted by an online English search using various electronic search databases. Predefined key-words for the pathogenesis of obesity-induced inflammation and associated diseases, as well as the role of various inflammatory molecules, were used. RESULTS: We have summarized the data of the articles consulted in this research and we have found that obesity is associated with a low-grade inflammation resulting from the change of adipose tissue (AT). The AT produces a variety of inflammatory molecules called adipocytokines that are involved in the onset of systemic low-grade inflammation which is the link between obesity and associated-chronic abnormalities; such as insulin resistance, metabolic syndrome, cardiovascular disease (CVD), hypertension, diabetes, and some cancers. Also, we have searched all the inflammatory molecules involved in this pathogenesis and we have briefly described the role of 16 of them which are the most related to obesity-associated inflammation. The results have shown that there are inflammatory molecules that have a positive relationship with the pathogenesis of obesity-related diseases and others have a negative relationship with this pathogenesis. CONCLUSION: Inflammation plays a crucial role in the development of various metabolic-abnormalities related to obesity. In this regard, the management of obesity may help reduce the risk of cardiovascular disease and other metabolic complications by inhibiting inflammatory mechanisms.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Doenças Cardiovasculares/etiologia , Metabolismo Energético , Mediadores da Inflamação/metabolismo , Inflamação/etiologia , Obesidade/complicações , Tecido Adiposo/fisiopatologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Transdução de Sinais
14.
Clin Sci (Lond) ; 134(12): 1473-1474, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32579179

RESUMO

Adipose biology research has grown rapidly offering new insights into the physiological and pathophysiological roles of different body fat depots. This Thematic Collection of Clinical Science brings a well-rounded timely view of the recent development in this field. We highlight the state of the art on adipose tissue function/dysfunction in the context of cardiovascular and metabolic pathologies.


Assuntos
Tecido Adiposo/patologia , Doenças Cardiovasculares/patologia , Terapia de Alvo Molecular , Adipocinas/metabolismo , Humanos , Inflamação/patologia
15.
Metabolism ; 108: 154261, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32407726

RESUMO

BACKGROUND: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. METHODS: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. RESULTS: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. CONCLUSIONS: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Tecido Adiposo Marrom/metabolismo , Lipogênese/fisiologia , Proteínas/metabolismo , Adipócitos Bege/metabolismo , Células Cultivadas , Estudos Transversais , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Obesidade/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Proteína Desacopladora 1/metabolismo , Regulação para Cima/fisiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-32360289

RESUMO

The regulation of porcine subcutaneous (SC) and intramuscular (IM) fat deposition significantly affects pork quality and the lean meat percentage of the carcass, respectively. The adipokine C1q/tumor necrosis factor-related protein 6 (CTRP6), plays a significant role in regulating animal fat deposition. The purpose of this study was to understand the effects of CTRP6 gene knockdown in IM and SC adipocytes by RNA-seq analysis. A total of 1830 and 2936 differentially expressed genes (DEGs) were identified in SC and IM adipocytes, respectively. 844 were down- and 2092 were upregulated in SC adipocytes, while 648 were down- and 1182 were upregulated in IM adipocytes. Furthermore, 1778 DEGs were detected only in SC adipocytes, 672 DEGs only in IM adipocytes, and 1158 DEGs in both types of adipocytes. GO analysis indicated that DEGs involved in adipocyte differentiation were significantly enriched in both SC and IM adipocytes following treatment with CTRP6-siRNA. Moreover, KEGG pathway enrichment analysis revealed differences of metabolic regulation between IM and SC adipocytes. With CTRP6-silencing, the signaling pathways related to Ras and arachidonic acid metabolism were significantly enriched in IM adipocytes, while four other signaling pathways, encompassing the TNF, MAPK, p53 and adipokine pathway were specifically enriched in SC adipocytes. Interestingly, the effect of CTRP6-siRNA treatment was attenuated by the specific Ras activator ML-097 in IM adipocytes, while the specific p53 activator SJ-172550 had the corresponding effect in SC adipocytes. Altogether, we suggest that CTRP6 may be a differential regulator of the development and metabolism of IM and SC adipose tissues.


Assuntos
Adipocinas/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adipocinas/deficiência , Adipocinas/genética , Animais , Masculino , Transdução de Sinais , Suínos
17.
Clin Sci (Lond) ; 134(7): 827-851, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32271386

RESUMO

Major shifts in human lifestyle and dietary habits toward sedentary behavior and refined food intake triggered steep increase in the incidence of metabolic disorders including obesity and Type 2 diabetes. Patients with metabolic disease are at a high risk of cardiovascular complications ranging from microvascular dysfunction to cardiometabolic syndromes including heart failure. Despite significant advances in the standards of care for obese and diabetic patients, current therapeutic approaches are not always successful in averting the accompanying cardiovascular deterioration. There is a strong relationship between adipose inflammation seen in metabolic disorders and detrimental changes in cardiovascular structure and function. The particular importance of epicardial and perivascular adipose pools emerged as main modulators of the physiology or pathology of heart and blood vessels. Here, we review the peculiarities of these two fat depots in terms of their origin, function, and pathological changes during metabolic deterioration. We highlight the rationale for pharmacological targeting of the perivascular and epicardial adipose tissue or associated signaling pathways as potential disease modifying approaches in cardiometabolic syndromes.


Assuntos
Adipocinas/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Vasos Sanguíneos/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Pericárdio/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adiposidade/efeitos dos fármacos , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Pericárdio/metabolismo , Pericárdio/patologia , Pericárdio/fisiopatologia , Transdução de Sinais
19.
Sci Adv ; 6(13): eaay6721, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32232152

RESUMO

Stem cell-derived extracellular vesicles (EVs) offer alternative approaches to stem cell-based therapy for regenerative medicine. In this study, stem cell EVs derived during differentiation are developed to use as cell-free therapeutic systems by inducing tissue-specific differentiation. EVs are isolated from human adipose-derived stem cells (HASCs) during white and beige adipogenic differentiation (D-EV and BD-EV, respectively) via tangential flow filtration. D-EV and BD-EV can successfully differentiate HASCs into white and beige adipocytes, respectively. D-EV are transplanted with collagen/methylcellulose hydrogels on the backs of BALB/c mice, and they produce numerous lipid droplets in injected sites. Treatments of BD-EV attenuate diet-induced obesity through browning of adipose tissue in mice. Furthermore, high-fat diet-induced hepatic steatosis and glucose tolerance are improved by BD-EV treatment. miRNAs are responsible for the observed effects of BD-EV. These results reveal that secreted EVs during stem cell differentiation into white adipocytes or beige adipocytes can promote cell reprogramming.


Assuntos
Adipócitos Bege/citologia , Adipócitos Brancos/citologia , Técnicas de Reprogramação Celular , Reprogramação Celular , Vesículas Extracelulares/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Adipócitos Bege/metabolismo , Adipócitos Brancos/metabolismo , Adipogenia , Adipocinas/metabolismo , Animais , Diferenciação Celular , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , MicroRNAs/genética
20.
Clin Chim Acta ; 507: 31-38, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32283064

RESUMO

Obesity, defined as having a body mass index (BMI) greater than 30 kg/m2, has been verified to be associated with several health problems which are always grouped as metabolic syndrome. However, the underlying pathogenic mechanisms remain unclear. The hallmarks of obesity are dysfunctional changes in adipose tissue and dyslipidemia characterized by elevated serum levels of low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), and reduced serum levels of high density lipoprotein cholesterol (HDL-C). Currently, it is widely accepted that rather than being a reservoir for energy storage, the adipose tissue could also secrete multiple hormones and molecules, named adipokines. Notably, growing evidence has put forward that under obese status, the adipocytes are dysfunctional with excessive secretion of multiple pro-inflammatory adipokines, contributing to a chronic inflammatory reaction and promote the progression of metabolic and cardiovascular complications. Although some adipokines have been shown to be causally linked to various disease processes, the functions of other novel adipokines in modulating diseases are still not elucidated. In this review, we focus on the microenvironment of adipose tissue and how it influences obesity and cardiovascular disorders. We also summarize the role of adipokines in modulating systemic inflammatory responses that contribute to cardio-metabolic disorders.


Assuntos
Adipocinas/metabolismo , Síndrome Metabólica/metabolismo , Biomarcadores/metabolismo , Humanos , Síndrome Metabólica/epidemiologia , Risco
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