Early introduction of exercise prevents insulin resistance in postnatal overfed rats

Early childhood obesity increases the risk of developing metabolic diseases. We examined the early introduction of exercise in small-litter obese-induced rats (SL) on glucose metabolism in the epididymal adipose tissue (AT) and soleus muscle (SM). On day 3 post-birth, pups were divided into groups of ten or three (SL). On day 22, rats were split into sedentary (S and SLS) and exercise (E and SLE) groups. The rats swam three times/week carrying a load for 30 min. In the first week, they swam without a load; in the 2nd week, they carried a load equivalent to 2% of their body weight; from the 3rd week to the final week, they carried a 5% body load. At 85 days of age, an insulin tolerance test was performed in some rats. At 90 days of age, rats were killed, and blood was harvested for plasma glucose, cholesterol, and triacylglycerol measurements. Mesenteric, epididymal, retroperitoneal, and brown adipose tissues were removed and weighed. SM and AT were incubated in the Krebs-Ringer bicarbonate buffer, 5.5 mM glucose for 1 h with or without 10 mU/mL insulin. Comparison between the groups was performed by 3-way ANOVA followed by the Tukey post-hoc test. Sedentary, overfed rats had greater body mass, more visceral fat, lower lactate production, and insulin resistance. Early introduction of exercise reduced plasma cholesterol and contained the deposition of white adipose tissue and insulin resistance. In conclusion, the early introduction of exercise prevents the effects of obesity on glucose metabolism in adulthood in this rat model.

Mediator complexes regulate skeletal muscle metabolic function: a review / 药学学报

Mediator complexes involved in skeletal muscle metabolic processes have become a hot research topic in recent years. The mediator complex is a multi-protein complex which participates in transcription by bridging specific transcription factors and basal transcriptional machinery (RNA polymerase II). Mediator complexes are involved in regulating the expression of transcription factors related to skeletal muscle metabolism and muscle fiber transformation, such as PPARs and PGC1α. These mediators participate in skeletal muscle glucose metabolism by regulating glucose transporter GLUT4 and key transcription factors of metabolic pathways. In addition, they regulate metabolic diseases by regulating the expression of PPARγ, UCP-1 and other genes involved in skeletal muscle lipid metabolism and mitochondrial functions. This article reviews the mechanism and effects of mediator complexes on skeletal muscle metabolism.

Regulation and mechanism of glucocorticoids on skeletal muscle metabolism / 中国药理学通报

Glucocorticoids ( GCs) have important regulatory effects on skeletal muscle metabolism. GCs can inhibit skeletal muscle glucose uptake and glycogen synthesis, and improve blood glucose levels by inhibiting Pik3rl expression, inhibiting insulin signaling pathway, or promoting pyruvate dehydrogenase kinase 4 expression; GCs can inhibit skeletal muscle lipid metabolism , causing the accumulation of lipid metabolism intermediates diacylglycerol and ceramides, and inducing skeletal muscle insulin resistance; GCs can induce MuRFl and MAFbx expression by promoting FoxO expression, activating the ubiquitin-proteasome system and autophagy lysosome system, and activating oxidative stress system, or promote the protein decomposi-tion of skeletal muscle by up-regulating C/EBPp expression; GCs can also inhibit the mTOR pathway by promoting myostatin and Pik3rl expression and inhibit skeletal muscle protein synthesis by up-regulating KLF-15 expression. This article explores the effects of GCs on skeletal muscle metabolism and its molecular mechanisms by tracking the latest developments at home and a-broad, which will provide reference for the clinical application of GCs.

Total saponins of Panax japonicus improve cancer cachexia in mice through inhibiting inflammatory response mediated by NF-κB / 中国药理学通报

Aim To investigate the therapeutic effect of total saponins of Panax japonicus(SPJ)on cancer cach-exia in mice with colon adenocarcinoma. Methods BALB/c mice were subcutaneously inoculated with mu-rine colon adenocarcinoma CT26 cells to induce ca-chexia. The model animals were randomly divided into three groups: model group, SPJ low dose group and high dose group. Gavage started on the 4th day after inoculation, and the dosage regimen was as follows:the normal and model groups were given 10 mL·kg-1 saline, qd ×27; the low dose and high dose groups were treated with 20 and 60 mg·kg-1SPJ respective-ly, qd ×27. After treatment, the effects of SPJ on body weight, tibialis anterior muscle, gastrocnemius muscle,spleen and epididymal fat changes of cachexia mice were observed. HE and Western blot were used to measure the changes of cross section of gastrocnemius muscle fibers and the expression of NF-κB,PAX7 and MuRF1 protein level in the gastrocnemius and tibialis anterior muscle. Results Compared with model group, the administration of SPJ could effectively re-duce the weight loss (P <0.05), increase muscle mass (P<0.05) and decrease muscle tissue degrada-tion in cachexia mice. Meanwhile,SPJ significantly re-duced the levels of IL-1β and TNF-α in serum (P <0.05) and decreased the expression of NF-κB. Con-clusion SPJ can improve cancer cachexia in mice in a dose-dependent manner. The potential mechanism may be associated with the inhibition of NF-κB mediated in-flammatory factor expression.

Standardization of Serum Creatinine Levels in Healthy Dogs Related to Body Weight at the South Valley of Aburra, Colombia / Estandarización de los valores séricos de creatinina en perros sanos con relación al peso corporal en el sur del Valle de Aburra / Padronização de creatinina sérica em cães saudáveis em relação ao peso corporal, no sul do Vale do Aburrá

Currently there are no serum creatinine reference values in Colombia for healthy dogs related to body weight; there are only available foreign studies. The objective was to determine serum creatinine values in healthy dogs related to body weight at the South Valley of Aburra. There were sampled 320 healthy dogs and divided into three groups related to the body weight according to the Kennel Club classification as follows: 1-10 kg, 11-25 kg and over 25 kg. In order to determine their health status, their medical records were revised and a complete physical examination was performed. Subsequently, a blood sample was taken to measure the creatinine levels. Statistically significant differences were found (p<0.05) among the three groups. This article presents evidence to classify serum creatinine values related to body weight in dogs, which could allow veterinarians to have a better reference value for assessing kidney function.

Actualmente no se cuenta con valores de referencia de creatinina sérica en Colombia en caninos sanos con relación al peso corporal. Solo se tienen los estudios foráneos. El objetivo central fue determinar los valores séricos de creatinina en perros sanos según el peso corporal en el sur del Valle de Aburrá. Se muestrearon 320 perros clínicamente sanos, los cuales se dividieron en tres grupos según el peso corporal de acuerdo con la clasificación del Kennel Club, 1-10 kg, 11-25 kg y mayores de 25 kg. Se realizó análisis de la historia clínica y un examen físico completo para determinar su estado de salud. Posteriormente, se tomó la muestra de sangre para la medición de creatinina. Se encontraron diferencias estadísticas significativas (p < 0,05) entre los tres grupos. Este artículo presenta evidencia para clasificar los valores de creatinina sérica según el peso corporal, lo que permite a los médicos veterinarios tener un mejor referente para la evaluación de la función renal.

A medição da creatinina sérica é um dos parâmetros atualmente utilizados na prática clínica pra avaliar a função renal em cães, isto é possível já que a creatinina é um componente do metabolismo muscular a qual é filtrada livremente pelos glomérulos, permitindo deste jeito estabelecer de forma geral a taxa de filtração glomerular e assim mesmo a da função renal. Atualmente não há valores de referência pra creatinina sérica na Colômbia em cães saudáveis em relação ao peso corporal, só ha estudos estrangeiros. Objetivo: Determinar os valores séricos de creatinina em cães saudáveis segundo seu peso corporal no Sul do Valle do Aburra. Foram amostrados 320 cães saudáveis, os quais foram divididos em três grupos, segundo o peso corporal de acordo com a classificação do Kennel Club, 1-10 kg, 11-25 kg e mais de 25 kg. Foi realizada a análise da história clínica e um exame físico completo para determinar seu estado de saúde; em seguida, tomou-se a amostra de sangue para a medição da creatinina. Foram encontradas diferenças estatisticamente significativas (p < 0,05) entre os três grupos. Este artigo apresenta evidências para classificar valores de creatinina sérica segundo o peso corporal, o que poderia permitir aos médicos veterinários ter uma melhor referência ao avaliar a função renal.

Effects and mechanisms of calorie restriction on the contractile function of skeletal muscle from rats / 中国医师杂志

Objective To investigate the effects of calorie restriction (CR) for 4 weeks on twitch tension,titanic tension,and fatigue contraction induced by electrical stimulation in different kind skeletal muscles from rats and explore the possible mechanisms.Methods The rat model of CR was established by a limitation of 40％ calorie intake of control rats for 4 weeks,and then oral glucose tolerance test (OGTT) was performed.The soleus (SOL) and extensor digitorum longus (EDL) were isolated under anesthetization to detect twitch tension,titanic tension,and fatigue contraction induced by electrical stimulation.Adenosine triphosphate (ATP) content was measured by fluorescent enzymatic methods to reflect mitochondrial function.The ratio of mitochondrial gene COX Ⅰ and nuclear gene β-actin copy number was analyzed to evaluate mitochondrial biogenesis.Furthermore,the transcriptions of peroxisome proliferatoractivated receptor γ coactivator-1 (PGC-1α) and nuclear respiratory factor 1 (NRF1) genes,expressions of phosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK) and nitric oxide synthase (NOS) proteins,and nitric oxide (NO) content were determined in skeletal muscle.Results The blood glucose level at 30 min and area under the curve of blood glucose levels at various time points during OGTT were significantly decreased in the CR group compared to the control group.The twitch tension [(2.5 ± 0.15)N/cm2 vs (1.24±0.12)N/cm2,(2.66 ±0.21)N/cm2 vs (1.69 ±0.17)N/cm2,P ＜ 0.05],titanic tension [(10.43 ± 0.36) N/cm2 vs (8.06 ± 0.19) N/cm2,(11.35 ± 1.02) N/cm2 vs (8.12 ± 0.23) N/cm2,P ＜ 0.05],and fatigue contraction force in SOL and EDL from CR rats were significantly increased in association with increases of ATP content [(34.82 ±4.31)) mnol/mg protein vs (15.32 ± 1.94) nmol/mg protein,(30.82 ± 2.15) nmol/mg protein vs (12.32 ± 0.97) nmol/mg protein,P ＜ 0.05] and mitochondrial biogenesis (2.75 ± 0.20 vs 1.52 ± 0.06,1.32 ± 0.10 vs 0.84 ± 0.11,P ＜ 0.05) compared to control rats.CR for 4 weeks upregulated the transcriptions of PGC-1α and NRF genes as well as the phosphorylation of AMPK protein in SOL but not in EDL.Furthermore,CR also enhanced NOS expression and NO content in both skeletal muscles.Conclusions CR for 4 weeks can strengthen the contractile function of SOL and DL from rats,and the underlying mechanisms might be related to the upregulation of PGC-1α transcription and AMPK activation,resulting in the enhances of mitochondrial biogenesis and mitochondrial function in skeletal muscles.

Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n = 5) or HFD (n = 28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n = 5), HFD (high-fat diet, n = 7), HFDA (high-fat diet + aged garlic extract, n = 7), HFDE (high-fat diet + exercise, n = 7), and HFDEA (high-fat diet + exercise + aged garlic extract, n = 7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

Amino Acids and Muscle Protein Metabolism with Aging / Jurnal Sains Kesihatan Malaysia

Sarcopenia is age-associated loss of skeletal muscle mass and strength which develops slowly over decades and becomes a significant factor to disability among the elderly population. Although several mechanisms of sarcopenia have been proposed, they all seem to affect the balance between muscle protein synthesis and breakdown, resulting in the net muscle loss. In present article, the most recent findings regarding the role of nutritional intake on muscle protein metabolism in the elderly will be reviewed. Particular focus will be given to dietary protein requirement for elderly, acute anabolic response of amino acids and protein intake, age-associated changes in the response of muscle protein to a meal intake, and the role of insulin resistance of muscle protein metabolism among the elderly. Finally, possible benefits and risks of protein and amino acid supplements for the prevention and treatment of sarcopenia will also be reviewed.

Assessment of Effect of Pulmonary Rehabilitation on Skeletal Muscle Metabolism by 31P Magnetic Resonance Spectroscopy / 결핵

Pulmonary rehabilitation has been known to improve dyspnea and exercise tolerance in patients with chronic lung disease, although it does not improve pulmonary function. The mechanism of this improvement is not clearly explained till now ; however some authors suggested that the improvement in the skeletal muscle metabolism after the rehabilitation could be a possible mechanism. The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation which causes early activation of anaerobic glycolysis and excess lactate production with exercise. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the improvement in the exercise tolerance after the rehabilitation, noninvasive 31P magnetic resonance spectroscopy(MRS) of the forearm flexor muscle was performed before and after the exercise training in nine patients with chronic lung disease who have undertaken intensive pulmonary rehabilitation for 6 weeks. 31P MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntary contraction(MVC) force of the muscle was measured before the isometric exercise, and then 30% of MVC force was constantly loaded to each patient during the isometric exercise. After the exercise training, exercise endurance of upper and lower extremities and 6 minute walking distance were significantly increased(p<0.05). There were no differences of baseline intracellular pH (pHi) and inorganic phosphate/phosphocreatine(Pi/PCr). After rehabilitation pHi at the exercise and the exhaustion state showed a significant increase(6.91+/-0.1 to 6.99+/-0.1 and 6.76+/-0.2 to 6.84+/-0.2 respectively, p<0.05). Pi/PCr at the exercise and the recovery rate of pHi and Pi/PCr did not show significant differences. These results suggest that the delayed intracellular acidosis of skeletal muscle may contribute to the improvement of exercise endurance after pulmonary rehabililtation.

Assessment of Abnormality in Skeletal Muscle Metabolism in Patients with Chronic Lung Desease by 31P Magnetic Resonance Spectroscopy / 결핵

The functional derangement of skeletal muscles which may be attributed to chronic hypoxia has been accepted as a possible mechanism of exercise impairment in patients with chronic obstructive pulmonary disease (COPD). The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation early activation of anaerobic glycolysis and excessive lactate and hydrogen ion production with exercise. But the cause of exercise limitation in patients with chronic lung disease without hypoxia has not been known. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the exercise limitation in chronic lung disease patients without hypoxia, we compared the muscular metabolic data of seven male patients which had been derived from noninvasive 31P magnetic resonance spectroscopy(MRS) with those of five age-matched normal male control persons. 31P MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntatry contraction(MVC) force of the muscle was measured before the isometric exercise, and the 30% of MVC force was constantly loaded to each patient during the isometric exercise. There were no differences of intracellular pH (pHi) and inorganic phosphate/phosphocreatine (Pi/PCr) at baseline, exhaustion state and recovery period between two groups. But pHi during the exercise was lower in patients group than the control group (p<0.05). Pi/PCr during the exercise did not show significant difference between two groups. These results suggest that the exercise limitation in chronic lung disease patients without hypoxia also could be attributed to the abnormalities in the skeletal muscle metabolism.