Mapping research in the obesity, adipose tissue, and microRNA field: a bibliometric analysis

Recent studies have investigated the control of adipose tissue expansion and inflammatory process by microRNAs (miRNAs). These two processes are of great interest because both are associated with obesity and metabolic syndrome. However, despite the great relevance of the role of miRNAs in obesity and adipose tissue, no qualitative and quantitative analysis on the subject has been performed. Thus, we aimed to examine global research activity and current trends with respect to the interaction between obesity, adipose tissue and miRNAs through a bibliometric analysis. This research was performed on the Scopus database for publications containing miRNA, obesity, and adipose tissue keyword combinations. In total, 898 articles were analyzed and the most frequently occurring keywords were selected and clustered into three well-defined groups. As a result, first group of keywords pointed to the research area on miRNAs expressed in obesity-associated diseases. The second group demonstrated the regulation of the adipogenesis process by miRNAs, while the third group highlighted brown adipose tissue and thermogenesis as one of the latest global research trends related to the theme. The studies selected in this paper describe the expression and performance of different miRNAs in obesity and comorbidities. Most studies have focused on identifying miRNAs and signaling pathways associated with obesity, type 2 diabetes mellitus, and cardiovascular disease. Thus, the miRNA profile for these diseases may be used as biomarkers and therapeutic targets in the prevention and treatment of obesity-associated diseases812CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP132365/2018-9sem informação17/09602-4; 2017/19504-

Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats

Role of aerobic physical training on the CSE/H 2 S/miR-34c-3p axis in the heart of healthy and hypertensive rats

A hipertensão arterial (HA), associa-se à importantes alterações estruturais, funcionais e moleculares no coração, dentre elas, a hipertrofia cardíaca (HC) do tipo patológica. Por outro lado, o treinamento físico (TF) aeróbico está associado às adaptações cardiovasculares benéficas, incluindo a HC fisiológica. Portanto, o TF têm sido investigado e utilizado como uma importante ferramenta terapêutica não-farmacológica tanto para tratamento quanto prevenção nas doenças cardíacas. O sulfeto de hidrogênio (H 2 S), o mais recente gasotransmissor reconhecido, é produzido endogenamente nos tecidos, sendo a cistationina-gama liase (CSE), a principal enzima responsável pela sua síntese no coração, exercendo papel cardioprotetor no sistema cardiovascular. Recentes evidências demonstram que os efeitos protetores do H 2 S podem ser mediados pelos microRNAS (miRNAS) e vice-versa. Os miRNAs são uma nova classe de moléculas reguladoras de RNAs, conservados e não codificadores de proteína, e estão emergindo como potenciais alvos terapêuticos para as doenças cardiovasculares. Está bem estabelecido que os miRNAs são dinamicamente regulados pelo exercício físico. Neste sentido, publicações de nosso grupo de pesquisa já mostraram que dois protocolos de TF em natação (5x semana/10 semanas), promovem HC fisiológica no VE de ratas normotensas, a qual foi associada à melhora da função cardíaca. Os dois protocolos de treinamento (P1 e P2), diferem-se somente pelo volume, sendo o P1 de menor volume e o P2, maior volume de treino. Dados prévios de micro-array (ainda não publicados) do nosso laboratório, realizados no VE destas ratas, mostrou uma pronunciada redução na expressão do miRNA-34c-3p nos grupos treinados, em comparação ao grupo controle, o que motivou o nosso estudo. Portanto, a proposta deste estudo treinamento físico aeróbico exerce seus efeitos benéficos e terapêuticos, por meio de regulação do eixo CSE/H2S/miR-34c-3p no coração, tanto em modelo de ratas saudáveis, como em modelo de ratos espontaneamente hipertensos (SHR). Para isso, este estudo foi dividido em duas etapas, onde na 1 a etapa serão utilizadas ratas normotensas Wistar (10 semanas de vida) submetidas aos protocolos de TF aeróbico e no segundo utilizamos o modelo de ratos SHR que foram submetidos ao mesmo protocolo experimentalArterial hypertension (AH) is associated with important structural, functional and molecular changes in the heart, including pathological cardiac hypertrophy (HC). On the other hand, aerobic physical training (ET) is associated with beneficial cardiovascular adaptations, including physiological GH. Therefore, TF has been investigated and used as an important non-pharmacological therapeutic tool for both the treatment and prevention of heart disease. Hydrogen sulfide (H2S), the most recent recognized gas transmitter, is produced endogenously in tissues, with cystathionine-gamma lyase (CSE), the main enzyme responsible for its synthesis in the heart, playing a cardioprotective role in the cardiovascular system. Recent evidence demonstrates that the protective effects of H2S can be mediated by microRNAS (miRNAS) and vice versa. miRNAs are a new class of conserved, non-protein-coding RNA regulatory molecules and are emerging as potential therapeutic targets for cardiovascular disease. It is well established that miRNAs are dynamically regulated by exercise. In this sense, publications by our research group have already shown that two swimming TF protocols (5x week/10 weeks) promote physiological CH in the LV of normotensive rats, which was associated with improvement in cardiac function. The two training protocols (P1 and P2) differ only in terms of volume, with P1 having a smaller volume and P2 having a greater training volume. Previous micro-array data (not yet published) from our laboratory, performed in the LV of these rats, showed a pronounced reduction in the expression of miRNA-34c-3p in the trained groups, compared to the control group, which motivated our study. Therefore, the purpose of this study is aerobic exercise training exerts its beneficial and therapeutic effects, through regulation of the CSE/H2S/miR-34c-3p axis in the heart, both in a healthy rat model and in aspontaneously hypertensive rat model (SHR). For this, study was divided into two stages, where in the 1st stage, normotensive Winstar rats (10 weeks of life) will be used submitted to aerobic TF protocols, and in the second stage, we use the SHR rat model submitted to the same experimental protoco

Ovariectomia e treinamento resistido: influência na morfologia e angiogênese do tecido adiposo visceral de ratas

Ovariectomy in animals (surgical removal of ovaries) is a model used to mimic the menopause in women. The ovarian hormone deficiency alters the lipid profile, increases inflammation and the risk of type 2 diabetes mellitus, sarcopenia, osteopenia, obesity and cardiovascular diseases. Resistance training (RT) has been used as a non-pharmacological tool to prevent or reverse the postmenopausal effects. However, there are few studies evaluating the ovariectomy (Ovx) and RT effects on the morphology and angiogenesis of visceral adipose tissue (VAT). Thus, the aim of this study was to investigate the Ovx and RT influence at the size and adipocytes number, gene expression and VEGF-A protein levels and microvessel density in VAT of rats. Adult Sprague-Dawley rats were divided into four groups (n=6 per group): Sham-operated sedentary (Sham-Sed), ovariectomized sedentary (Sed-Ovx), Sham-operated resistance training (Sham-Tr) and ovariectomized resistance training (Ovx- Tr). During the resistance training period, the animals climbed a 1.1m vertical ladder with weights attached to their tails, which were progressively increased; the sessions were performed three times a week, with 4-9 climbs and 8-12 dynamic movements per climb with intervals of 2 minutes between climbs. Histological analysis was performed to analyze vascular micro density and morphology of VAT; gene expression and VEGF-A protein levels were analyzed by real-time PCR and ELISA, respectively. Ovx resulted in higher body weight, adipocyte hypertrophy, decreased both VEGF-A mRNA and protein and VEGF-R2 mRNA expression, and decreased the micro vascular density in the VAT of sedentary rats. However, RT was not able to prevent any changes induced by ovariectomy. The data indicated that Ovx impaired the morphology and angiogenesis of rats VAT and that RT protocol adopted did not prevent these changes. We suggest future studies performing adaptations in this resistance training program, associated or not to hypocaloric diet and treatment with estradiol.Financiadora de Estudos e ProjetosA ovariectomia em animais (remoção cirúrgica dos ovários) é um modelo de estudo utilizado para mimetizar a menopausa em mulheres. A deficiência dos hormônios ovarianos altera o perfil lipídico, aumenta a inflamação e o risco de diabetes tipo 2, sarcopenia, osteopenia, obesidade e doenças cardiovasculares. O treinamento resistido (TR) tem sido empregado como ferramenta não farmacológica na tentativa prevenir ou reverter os efeitos da pósmenopausa. No entanto, são escassos os estudos sobre os efeitos da Ovx e TR na morfologia e angiogênese do tecido adiposo visceral (TAV). Diante disto, o objetivo desta pesquisa foi verificar a influência da Ovx e do TR no tamanho e no número dos adipócitos, expressão gênica e concentração proteica de VEGF-A e densidade microvascular do TAV de ratas. Ratas Sprague-Dawley adultas foram dividas em quatro grupos experimentais (n=6 por grupo): Sham operado sendentário (Sham-Sed); Ovariectomizado sedentário (Ovx-Sed); Sham operado treinamento resistido (Sham-Tr) e Ovariectomizado treinamento resistido (Ovx-Tr). Durante o período de treinamento resistido, os animais escalaram uma escada vertical de 1,1 m com pesos atados em suas caudas, que foram aumentados progressivamente; as sessões foram realizadas três vezes na semana, com 4-9 escaladas por sessão de treino e 8- 12 movimentos por escalada com intervalos de 2 minutos entre as escaladas. A morfologia e densidade vascular foram avaliadas por meio de análises histológicas, a expressão gênica e proteica do VEGF-A foram analisadas por PCR em tempo real e ELISA, respectivamente. A ovariectomia aumentou a massa corporal e provocou hipertrofia dos adipócitos, diminuição da expressão de VEGF-A e seu receptor, diminuição da concentração de VEGF-A e redução da densidade microvascular no TAV das ratas. O treinamento resistido não foi eficiente em prevenir nenhuma destas alterações. Sugere-se futuros estudos realizando adaptações neste programa de treinamento resistido, associadas ou não à dieta hipocalórica e ao tratamento com o estradiol

Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats