Regulation Of Gene Expression By Exercise-related Micrornas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Gene expression control by microRNAs ( miRs) is an important mechanism for maintenance of cellular homeostasis in physiological and pathological conditions as well as in response to different stimuli including nutritional factors and exercise. MiRs are involved in regulation of several processes such as growth and development, fuel metabolism, insulin secretion, immune function, miocardium remodeling, cell proliferation, differenciation, survival, and death. These molecules have also been proposed to be potential biomarkers and/or therapeutical targets in obesity, type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, and cancer. MiRs are released by most cells and potentially act on intercellular communication to borderer or distant cells. Various studies have been performed to elucidate the involvement of miRs in exercise-induced effects. The aims of this review are: 1) to bring up the main advances for the comprehension of the mechanisms of action of miRs; 2) to present the main results on miR involvement in physical exercise; 3) to discuss the physiological effects of miRs modified by exercise. The state of the art and the perspectives on miRs associated with physical exercise will be presented. Thus, this review is important for updating recent advances and driving further strategies and studies on the exercise-related miR research. (C) 2016 The Author(s) Published by S. Karger AG, Basel39623812397Sao Paulo State Research Foundation (FAPESP)Coordination for the Improvement of Higher Level Personnel (CAPES)National Council for Scientific and Technological Development (CNPq)National Institute of Science and Technology in Obesity and Diabetes (INOD)Office for Post-Graduate and Research of the Cruzeiro do Sul UniversityOffice for Research of the University of Sao PauloFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Macadamia Oil Supplementation Attenuates Inflammation and Adipocyte Hypertrophy in Obese Mice

Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Dept Biol Celular & Desenvolvimento, BR-05508000 São Paulo, BrazilUniv Estadual Paulista, UNESP, Dept Educ Fis, Programa Posgrad Ciencia Motricidad, BR-13506900 Rio Claro, SP, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 São Paulo, BrazilUniv Sao Judas Tadeu, Dept Ciencias Biol, Lab Movimento Humano, BR-05503001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fisiol, Disciplina Fisiol Nutr, BR-04023901 São Paulo, BrazilUniv São Paulo, Inst Biociencias, Dept Fisiol Geral, BR-05508090 São Paulo, BrazilUniv Cruzeiro Sul, Inst Ciencias Atividade Fis & Esporte, Programa Posgrad Ciencia Movimento Humano, BR-01506000 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fisiol, Disciplina Fisiol Nutr, BR-04023901 São Paulo, BrazilWeb of Scienc

Sunflower Oil Supplementation Has Proinflammatory Effects and Does Not Reverse Insulin Resistance in Obesity Induced by High-Fat Diet in C57BL/6Mice

High consumption of polyunsaturated fatty acids, such as sunflower oil has been associated to beneficial effects in plasma lipid profile, but its role on inflammation and insulin resistance is not fully elucidated yet. We evaluated the effect of sunflower oil supplementation on inflammatory state and insulin resistance condition in HFD-induced obese mice. C57BL/ 6 male mice (8 weeks) were divided in four groups: (a) control diet (CD), (b) HFD, (c) CD supplemented with n-6 (CD + n-6), and (d) HFD supplemented with n-6 (HFD + n-6). CD + n-6 and HFD + n-6 were supplemented with sunflower oil by oral gavage at 2 g/ Kg of body weight, three times per week. CD and HFD were supplemented with water instead at the same dose. HFD induced whole andmuscle-specific insulin resistance associated with increased inflammatory markers in insulin-sensitive tissues andmacrophage cells. Sunflower oil supplementation was not efficient in preventing or reducing these parameters. In addition, the supplementation increased pro-inflammatory cytokine production by macrophages and tissues. Lipid profile, on the other hand, was improved with the sunflower oil supplementation in animals fed HFD. In conclusion, sunflower oil supplementation improves lipid profile, but it does not prevent or attenuate insulin resistance and inflammation induced by HFD in C57BL/ 6 mice.Sao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)Coordination for the Improvement of Higher Level Personnel (CAPES)Coordination for the Improvement of Higher Level Personnel (CAPES)National Council for Scientific and Technological Development (CNPq)/National Institute of Science and Technology in Obesity and Diabetes (INOD)National Council for Scientific and Technological Development (CNPq)/National Institute of Science and Technology in Obesity and Diabetes (INOD)Center of Lipid Research and Education (CLEaR)Center of Lipid Research and Education (CLEaR)Dean's Office for Research/University of Sao PauloDeans Office for Research/University of Sao Paul

Effects of fatty acids on endothelial cell death.

Foram avaliados: morte celular, conteúdo intracelular de NO e produção de ERO, em células endoteliais (ECV-304). Foram estudados os ácidos graxos: esteárico (SA) a 150 mM, oléico (OA) a 300 mM e linoléico (LA), gama-linolênico (gA), EPA e DHA a 50 e 100 mM. O SA induziu morte em 17,8 % das células, aumentou 99,2 % as ERO e não alterou o NO. O SA com os AG w-3 não alterou a morte induzida pelo SA. O DHA a 50 mM com o SA diminuiu 58 % o NO e EPA a 50 e 100 mM reduziu 78,4 % e 50%, respectivamente. O SA com DHA e EPA a 100 mM diminuiu as ERO em 20 %. Os AG w-6 (LA e gA) aboliram a morte induzida pelo SA. O LA a 100 mM aumentou o NO em 32,5 % e esse a 50 e 100 m M reduziu 50 % e 67 %, respectivamente, as ERO. O OA não alterou a viabilidade celular e as ERO, mas diminuiu o NO em 57 %. O OA com os AG w-3 e w-6 causou morte em 84 % das células, reduziu o NO em 60 % sem alterar as ERO. Assim, AG w-6 protegem contra a morte induzida por AG saturado. O OA não é tóxico mesmo em altas concentrações. Contudo, quando associado aos AG w-3 e w-6 pode causar citotoxicidade.The parameters examined were: cell death, intracellular content of NO and production of ROS, on endothelial cells (ECV-304). The fatty acids studied were: stearic (SA) at 150 mM, oleic (OA) at 300 mM, linoleic (LA), gamma-linolenic (gA), EPA and DHA at 50 and 100 mM. SA led 17.8% of cells to death, increased by 99.2% ROS and did not alter the NO. SA with w-3 PUFA did not alter dead cells induced by SA. DHA at 50 mM plus SA decreased NO by 58% and EPA at 50 e 100 mM reduced by 78.4% and 50%, respectively. SA with DHA or EPA at 100 mM decreased ROS at 20 %. w-6 PUFA, LA and gA, abolished cell death induced by SA. LA at 100 mM increased NO by 32.5% and this PUFA at 50 e 100 mM decreased ROS by 50% and 67%, respectively. OA did not alter cell viability and ROS but decreased the NO by 57%. OA with w-3 and w-6 PUFA increased dead cells to 84 %, decreased NO by 60 % and did not alter ROS. Thus, w-6 PUFA protect against cell death induced by saturated FA. OA is not toxic even at high concentrations. However, when associated with PUFA (w-3 e w-6) OA causes cytotoxicity

Peripheral insulin-sensitivity and inflammation response under obesogenic diets, fish oil supplementation and absence of TLR-4.

O objetivo desse estudo foi investigar a associação da inflamação com a resistência periférica à insulina (RI) na vigência de dietas obesogênicas, suplementação com óleo de peixe (SOP) e ausência de TLR-4. Os animais receberam dieta balanceada (DB), DB e leite condensado (DB+LC), hiperlipídica (HFD) ou HFD+LC. DB+LC e HFD levaram ao aumento: no ganho de massa corpórea (MC) e expressão de F4/80 e leptina no tecido adiposo (TA) em relação à DB. Em relação à HFD, HFD+LC provocou: aumento no HOMA-IR (4x), nos conteúdos de IL-6, IL-10, TNF-a, IL-1b, ICAM-1, VCAM-1 e leptina no TA. Comparada à DB+LC, HF+LC aumentou: a MC, HOMA-IR e expressão de F4/80 e reduziu a expressão de leptina no TA. A SOP nos animais em DB reduziu a expressão de F4/80, TNF-a e TLR-4 no fígado. A SOP em HFD reduziu o MC, HOMA-IR e aumentou o conteúdo de adiponectina no TA. A deleção de TLR-4 elevou o MC em DB+OP e a gordura mesentérica no HFD+OP. Assim, o consumo elevado de gordura ou açúcar causou obesidade e a associação de ambos potencializou a obesidade e induziu RI e inflamação no TA. A suplementação com OP atenuou a inflamação associada à DB e a obesidade e RI na vigência de HFD, sendo esses efeitos dependentes de TLR-4.The aim of this study was to investigate the association between inflammation and insulin resistance (IR) under obesogenic diets, fish oil supplementation (FOS) and TLR-4-/-. The mice were fed a balanced diet (BD), BD and condensed milk (BD+CM), high-fat diet (HFD) or high-fat diet and condensed milk (HFD+CM). The BD+CM and HFD increased: body weight gain (BWG), F4/80 and leptin in adipose tissue (AT). The HFD+CM compared to HFD increased: HOMA-IR, the contents of IL-6, IL-10, TNF-a, IL-1b, ICAM-1, VCAM-1 and leptin in AT. As compared to BD+CM, HFD+CM increased: BWG, HOMA-IR, F4/80 and reduced the leptin in AT. The FOS+BD reduced F4/80, TNF-a and TLR-4 in the liver. The FOS+HFD reduced BWG, HOMA-IR and increased the adiponectin in AT. TLR-4 deletion increased BWG in the FOS+BD and mesenteric fat in the FOS+HFD groups. The high consumption of fat or sugar induced obesity and the association of both potentiated this effect leading to IR and inflammation in adipose tissue and perivascular fat. FO supplementation attenuated the inflammation when associated with BD and the obesity and IR induced by HFD in a TLR-4 dependent-manner

A influência dos ácidos graxos trans na disfunção da célula endotelial e o possível efeito terapêutico do exercício sobre o tecido endotelial como forma de prevenção ou regressão da aterosclerose

O endotélio atua ativamente na regulação do tônus vascular, sintetizando e liberando substâncias vasoativas. A inflamação e os fatores de risco cardiovasculares alteram a homeostase vascular, levando à disfunção endotelial e possível formação de placas de ateroma. O aumento das concentrações plasmáticas de ácidos graxos livres pode causar lipotoxicidade vascular, disfunção do endotélio e, finalmente, aterosclerose. Dieta rica em lipídeos contendo ácidos graxos trans tem correlação positiva com a progressão de doenças cardiovasculares. Mudanças no estilo de vida, na adoção de dieta balanceada e atividade física são estratégias para a prevenção de doenças cardiovasculares e a reabilitação de pacientes. Nesta revisão, discutimos a influência benéfica do exercício físico em aspectos importantes da disfunção endotelial causados pelos ácidos graxos trans, incluindo evidências recentes e/ou ainda não exploradas. Discutimos também quais seriam os mecanismos envolvidos no comprometimento funcional da célula endotelial frente ao aumento de ácidos graxos trans na circulação

Toxicity of fatty acids on ECV-304 endothelial cells

AbstractThe effects of stearic (saturated) or oleic (monounsaturated) acids and their combination with ω-3 and ω-6 polyunsaturated fatty acids (PUFA) on death of endothelial cells (ECV-304 cell line) were investigated. We examined: loss of plasma membrane integrity, DNA fragmentation, accumulation of neutral lipids (NL) and release of reactive oxygen species (ROS). The fatty acids studied were: stearic (SA), oleic (OA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic (LA) and gamma-linolenic (γA) acids. SA at 150μM induced cell death, did not lead to accumulation of NL and raised the release of ROS. ω-3 PUFA decreased ROS production, increased NL content but did not protect against ECV-304 cell death induced by SA. ω-6 PUFA inhibited SA-induced cell death, increased NL content and decreased ROS production. OA caused cell death but did not increase NL content and ROS production even at 300μM. ω-3 and ω-6 FA associated with OA further increased cell death with no change in ROS production and NL content. Concluding, ω-6 PUFA had a greater protective effect than ω-3 PUFA on the deleterious effects caused by SA whereas OA had low cytotoxicity but, when associated with PUFA, presented marked toxic effects on ECV-304 endothelial cells

Inflammatory state of periaortic adipose tissue in mice under obesogenic dietary regimens

High-fat diet or high-sugar diet causes obesity and a chronic low-grade inflammation that leads to the development of diabetes and cardiovascular diseases. Inflammation of the surrounding fat of thoracic aorta namely periaortic adipose tissue (PAAT) has been associated with increased prevalence of vascular diseases in obesity. C57Bl/6 male mice (12 weeks of age) fed a whole grain-based commercial diet (WGD), refined carbohydrate diet (RCD), refined carbohydrate diet plus sweetened condensed milk ad libitum (RCD + CM) or high-fat diet (HFD) for eight weeks were studied. Serum fatty acid (FA) composition was evaluated by gas chromatography. The cellularity (as indicated by DNA and protein contents) and the inflammatory state (as indicated by the contents of TNF-α, IL-6, IL-1β, IL-10, VCAM-1, ICAM-1, leptin and adiponectin measured by ELISA) of the PAAT and thoracic aorta (TA) were evaluated. Both obesogenic regimens (RCD + CM and HFD) increased the content of total fatty acids (FA) in serum and the cellularity of the PAAT compared to WGD. RCD + CM increased serum monounsaturated fatty acid (MUFA) levels and HFD increased serum saturated fatty acid (SFA) levels compared to WGD. RCD (one of the diets used as control) and RCD + CM increased the levels of TNF-α, IL-1β, IL-10 and VCAM-1 in the PAAT compared to WGD. Mice fed with HFD showed decreased contents of TNF-α, VCAM-1 and IL-10 in the PAAT compared to animals fed RCD. The RCD raised the levels of SFA in serum, cellularity and inflammatory state in the PAAT compared to WGD. In conclusion, the effects of obesogenic dietary regimens on PAAT can be interpreted differently when the results are compared with WGD or RCD. We found marked changes in the PAAT and no significant modifications in TA indicating this adipose tissue as the major starting point of vascular diseases

Liver Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate Diet or High-Fat Diet

Both high-carbohydrate diet (HCD) and high-fat diet (HFD) modulate liver fat accumulation and inflammation, however, there is a lack of data on the potential contribution of carbohydrates and lipids separately. For this reason, the changes in liver fatty acid (FA) composition in male Swiss mice fed with HCD or HFD were compared, at the time points 0 (before starting the diets), and after 7, 14, 28 or 56 days. Activities of stearoyl-CoA desaturase-1 (SCD-1), ∆-6 desaturase (D6D), elongases and de novo lipogenesis (DNL) were estimated. Liver mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was evaluated as an additional indicator of the de novo lipogenesis. Myeloperoxidase activity, nitric oxide (NO) production, and mRNA expressions of F4/80, type I collagen, interleukin (IL)-6, IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) were measured as indication of the liver inflammatory state. The HCD group had more intense lipid deposition, particularly of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This group also showed higher DNL, SCD-1, and D6D activities associated with increased NO concentration, as well as myeloperoxidase activity. Livers from the HFD group showed higher elongase activity, stored more polyunsaturated fatty acids (PUFAs) and had a lower omega-6/omega-3 fatty acid (n-6/n-3) ratio. In conclusion, liver lipid accumulation, fatty acids (FA) composition and inflammation were modulated by the dietary composition of lipids and carbohydrates. The HCD group had more potent lipogenic and inflammatory effects in comparison with HFD