Can maternal physical activity modulate the nutrition-induced fetal programming?

Existe considerável evidência para a indução de diferentes fenótipos em reposta às variações no ambiente fetal e neonatal. O aporte inadequado de nutrientes no período crítico do desenvolvimento está associado ao risco alto de doenças metabólicas na vida adulta, este fenômeno biológico é chamado de programação. A atividade física durante a gestação resulta em adaptações fisiológicas da mãe e no aumento da disponibilidade de nutrientes e oxigênio no espaço feto-placentário. Este trabalho tem como objetivo discutir os mecanismos da indução de programação fetal pela nutrição e o provável efeito modulador da atividade física durante a gestação. Foram utilizadas as bases de dados do Medline Pubmed, Lilacs e Bireme, com publicações entre 1990 até 2008. Os termos de indexação utilizados foram: nutrition, fetal programming, gestation, physical activity, physical exercise, metabolism. Em conclusão, o aporte inadequado de nutrientes programa o aparecimento de doenças metabólicas na vida adulta, enquanto que a atividade física durante a gestação aumenta a disponibilidade de nutrientes e oxigênio, repercutindo positivamente no crescimento fetal e no peso ao nascer.There is considerable evidence for the induction of different phenotypes by variations in fetal and neonatal environment. Undernutrition during this critical development period is associated with risk of metabolic disease in adult life; this biological phenomenon is termed programming. Physical activity during gestation results in maternal physiological adaptations and increased oxygen and nutrients in the fetoplacental compartment. The main goal of this work is to discuss the mechanisms of fetal programming induced by nutrition and the probable modulating effect of physical activity during gestation. Papers published between 1990 and 2008 listed in the Medline Pubmed, Lilacs and Bireme databases were used. The search keywords were: nutrition, fetal programming, gestation, physical activity, physical exercise, and metabolism. In conclusion, undernutrition can program the onset of metabolic diseases in adult life, while physical activity during gestation increases the availability of nutrients and oxygen for the fetus, thereby positively impacting fetal growth and birth weight

Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function

Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms

Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated-skeletal muscle insulin resistance

Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation

Deletion of kinin B2 receptor alters muscle metabolism and exercise performance

Metabolic syndrome is a cluster of metabolic risk factors such as obesity, diabetes and cardiovascular diseases. Mitochondria is the main site of ATP production and its dysfunction leads to decreased oxidative phosphorylation, resulting in lipid accumulation and insulin resistance. Our group has demonstrated that kinins can modulate glucose and lipid metabolism as well as skeletal muscle mass. By using B2 receptor knockout mice (B2R-/-) we investigated whether kinin action affects weight gain and physical performance of the animals. Our results show that B2R-/- mice are resistant to high fat diet-induced obesity, have higher glucose tolerance as well as increased mitochondrial mass. These features are accompanied by higher energy expenditure and a lower feed efficiency associated with an increase in the proportion of type I fibers and intermediary fibers characterized by higher mitochondrial content and increased expression of genes related to oxidative metabolism. Additionally, the increased percentage of oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is coupled with a higher aerobic exercise performance. Taken together, our data give support to the involvement of kinins in skeletal muscle fiber type distribution and muscle metabolism, which ultimately protects against fat-induced obesity and improves aerobic exercise performance

Metabolic regulation and production of oxygen reactive species during muscule contraction: effect of glycogen on intracellular redox state

O exercício físico prolongado reduz os estoques de glicogênio muscular. Nessas condições, os processos de fadiga muscular são estimulados coincidindo com um aumento na produção de espécies reativas de oxigênio. A suplementação de carboidratos ou de antioxidantes isoladamente contribui para a melhora da performance muscular, sugerindo um efeito importante da depleção de substrato (glicose) e do aumento da produção de EROs no desenvolvimento da fadiga muscular durante a atividade física. Embora o mecanismo seja desconhecido, estamos propondo neste estudo que uma maior disponibilidade de glicogênio poderia favorecer uma maior atividade da via das pentoses fosfato, aumentando a disponibilidade de NADPH e GSH no tecido muscular esquelético. Uma maior capacidade antioxidante aumentaria a capacidade do tecido muscular em atividade, mantendo o equilíbrio redox durante atividade física prolongada e melhorando o desempenho. Neste processo, o ciclo glicose-ácido graxo pode ser importante aumentando a oxidação de lipídio e reduzindo o consumo de glicogênio durante a atividade prolongada. Além disso, um aumento na produção de EROs pode reduzir a atividade de enzimas importantes do metabolismo celular incluindo a aconitase e a a-cetoglutarato desidrogenase, comprometendo a produção de energia oxidativa, via predominante na produção de ATP durante a atividade muscular prolongada.Fatigue is closely related to the depletion of glycogen in the skeletal muscle during prolonged exercise. Under this condition, the production of oxygen reactive species (ROS) is substantially increased. It has been shown that dietary supplementation of carbohydrate or antioxidant attenuates muscle fatigue during contraction. This suggests that glycogen availability and/or elevated ROS production plays an important role on muscle fatigue development during prolonged muscle activity. Although the mechanism is still unknown, we propose that elevated muscle glycogen availability may lead to a high activity of hexose monophosphate pathway, increasing the NADPH and glutathione concentration in the skeletal muscle tissue. Elevated antioxidant capacity would increase the muscle redox balance during muscle contraction, improving performance. In this process, the glucose-fatty acid cycle may be important to increase lipid oxidation and consequently decrease glycogen utilization during prolonged activity. In addition, an elevated ROS production could reduce the activity of key metabolic enzymes including aconitase and a-ketoglutarate dehydrogenase, decreasing the oxidative energy production in the skeletal muscle during prolonged activity.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

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

Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction

O ciclo glicose-ácido graxo explica a preferência do tecido muscular pelos ácidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercício de alta intensidade, há aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espécies reativas de oxigênio (EROs) durante a atividade muscular sugere que o balanço redox intracelular é importante na regulação do metabolismo de lipídios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteína desacopladora mitocondrial. O efeito oposto é esperado durante a atividade moderada. Assim, as questões levantadas nesta revisão são: Por que o músculo esquelético utiliza preferencialmente os lipídios no estado basal e de atividade moderada? Por que o ciclo glicose-ácido graxo falha em exercer seus efeitos durante o exercício intenso? Como o músculo esquelético regula o metabolismo de lipídios e carboidratos em regime envolvendo o ciclo contração-relaxamento555303313CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãoThe glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle