The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids.

PURPOSE:The objective of the present study was to analyze the physiological and metabolic changes occurring in rats subjected to high-fat diet for one month. METHODS:The animals received a modified AIN-93 diet with increased lipid content and decreased carbohydrate content, while the control group received the normal AIN-93 diet. RESULTS: It was observed that the high-fat diet did not induce weight gain but led to greater gain of hepatic fat compared to control. Biochemcal parameters, glycemia, total cholesterol and serum protein did not differ between groups. In parallel, rats receiving the high-fat diet consumed less feed. CONCLUSION: The development of obesity through high-fat diet is associated with increased energy intake and time of exposure to the diet, while the metabolic syndrome is more associated with the combination of a diet rich in fat and carbohydrates. Key words: Obesity. Lipids. Hyperphagia. Weight Gain. Rats. RESUMO OBJETIVO:Analisar modificações fisiológicas e metabólicas em ratos submetidos à dieta hiperlipídica por um mês. MÉTODOS: Os animais receberam a dieta AIN-93 modificada, com aumento do teor de lipídeos e diminuição do teor de carboidratos, enquanto o grupo controle recebeu a dieta AIN-93. RESULTADOS: Foi observado que a dieta hiperlipídica não induziu o ganho de peso, porém levou a um maior ganho de gordura hepática, em comparação ao grupo controle. Os parâmetros bioquímicos, glicemia, colesterol total e proteína sérica não diferiram entre os grupos. Ao mesmo tempo os ratos alimentados com dieta hiperlipídica, apresentaram uma menor ingestão de alimentos. CONCLUSÃO: O desenvolvimento da obesidade com a dieta hiperlipídica está associado com aumento da ingestão de energia e tempo de exposição à dieta, enquanto a síndrome metabólica está mais associada a dietas com alto teor de gordura e carboidratos, concomitantemente. Descritores: Obesidade. Lipídeos. Hiperfagia. Ganho de peso. Ratos. Picchi MG et al.

Estrogen reduction is associated with a decline in skeletal muscle mitochondrial biogenesis. Molecular events associated with improvements in markers of mitochondrial biogenesis after resistance training and estradiol replacement are unknown. This study aimed to investigate the effects of ovariectomy, resistance training, and estradiol replacement on markers of mitochondrial biogenesis and protein expression related to oxidative capacity in the rat gastrocnemius pool. Estradiol replacement was performed using Silastic(®) capsules. During the 12-week resistance training, animals climbed a ladder with weights attached to their tails. Gene expression was analysed by RT-PCR, and protein content was determined by western blotting. Ovariectomy decreased the gene expression of the mitochondrial biogenesis markers PGC-1α (~73%), NRF-1 (~44%), and TFAM (~53%) (p<0.05) and decreased the protein expression of phosphorylated AMPK, CREB and AKT, which are related to oxidative capacity. Resistance training increased PGC-1α (~59%) and TFAM (~48%) expression compared to the Ovariectomy-Sedentary group. The combination of resistance training and estradiol replacement was superior to the ovariectomy-sedentary and ovariectomy-resistance training treatments regarding the gastrocnemius muscle. Estrogen deficiency altered the expression of genes and proteins that favour the development of a mitochondrial dysfunction phenotype, which was improved with resistance training and was partially improved by estradiol replacement.

SUMMARYThe 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? (1) propuseram a existência de uma competição entre glicose e ácidos graxos (AG) como substratos para a síntese de ATP no músculo esquelético, cardíaco e adipócitos. Nesse processo, foi demonstrado que, sob elevada disponibilidade de lipídios, os músculos esqueléticos utilizam predominantemente AG para a síntese e obtenção de ATP. Em contraste, sob elevada disponibilidade de carboidratos, utilizam predominantemente glicose. A questão que surge é qual a importância fisiológica dessa regulação entre glicose e ácidos graxos? Podemos encontrar uma respos-

Estrogen deficiency is directly related to central obesity and low-grade inflammation. Hormonal replacement and exercise training are both able to decrease fat accumulation and inflammation in postmenopausal women. However, the efficiency of resistance training (RT) and estrogen replacement (ER) in minimizing adiposity and inflammation in the visceral adipose tissue (VAT) of ovariectomized (OVX) rats has not yet been elucidated. In this study, Sprague-Dawley rats were divided into the following 6 groups: sham-operated sedentary (Sham-Sed), OVX-Sed, Sham-RT, OVX-RT, OVX-Sed-ER, and OVX-RT-ER groups. ER was performed by implanting silastic capsules containing 17β-estradiol. For RT, the animals were required to climb a 1.1-m vertical ladder with conical flasks containing weights attached to their tails for 12 weeks. Histological analyses were used to evaluate morphological changes. Gene expression levels were determined by quantitative real-time reverse transcriptase polymerase chain reaction, and protein concentrations were determined using Multiplex/Luminex assays. Ovariectomy increased the body mass (BM), adipocyte area, and inflammation in the VAT, the latter of which was indicated by reduced interleukin-10 (48%) and increased tumor necrosis factor (TNF)-α concentration (∼3%). RT efficiently decreased BM, adipocyte area, and inflammation in the OVX groups. The combination of RT and ER decreased BM (19%) and the TNF-α concentration (18%) and increased the gene and protein expression levels of adiponectin (173% and 18%). These results indicate that RT and the combination of RT and ER are efficient strategies for reducing the BM and improving the inflammatory status of OVX rats.