Sphingosine Kinase 1 Is Regulated by Peroxisome Proliferator-activated Receptor α in Response to Free Fatty Acids and Is Essential for Skeletal Muscle Interleukin-6 Production and Signaling in Diet-induced Obesity

We previously demonstrated that sphingosine kinase 1 (Sphk1) expression and activity are up-regulated by exogenous palmitate (PAL) in a skeletal muscle model system and in diet-induced obesity in mice; however, potential functions and in vivo relevance of this have not been addressed. Here, we aimed to determine the mechanism by which PAL regulates SphK1 in muscle, and to determine potential roles for its product, sphingosine-1-phosphate (S1P), in muscle biology in the context of obesity. Cloning and analysis of the mouse Sphk1 promoter revealed a peroxisome proliferator-activated receptor (PPAR) α cis-element that mediated activation of a reporter under control of the Sphk1 promoter; direct interaction of PPARα was demonstrated by chromatin immunoprecipitation. PAL treatment induced the proinflammatory cytokine interleukin (IL)-6 in a manner dependent on SphK1, and this was attenuated by inhibition of the sphingosine-1-phosphate receptor 3 (S1PR3)_. Diet-induced obesity in mice demonstrated that IL-6 expression in muscle, but not adipose tissue, increased in obesity, but this was attenuated in Sphk1^−/− mice. Moreover, plasma IL-6 levels were significantly decreased in obese Sphk1^−/− mice relative to obese wild type mice, and muscle, but not adipose tissue IL-6 signaling was activated. These data indicate that PPARα regulates Sphk1 expression in the context of fatty acid oversupply and links PAL to muscle IL-6 production. Moreover, this function of SphK1 in diet-induced obesity suggests a potential role for SphK1 in obesity-associated pathological outcomes.     

三角鲂和长春鳊肌肉营养成分分析与品质评价

用常规方法测定、分析了三角鲂(Megalobrama tarminalis)和长春鳊(Parabramis pekinensis肌肉中营养成分组成与含量.结果显示,三角鲂肌肉蛋白质、脂肪含量分别为18.19％和3.06％,长春鳊肌肉蛋白质、脂肪含量分别为19.38％和2.89％.三角鲂和长春鳊肌肉中均检测出18种氨基酸,其中包括了8种人体必需氨基酸.三角鲂肌肉中氨基酸总量为76.27％,其中,8种人体必需氨基酸含量为32.17％,占氨基酸总量的42.18％;长春鳊肌肉中氨基酸总量为77.60％,其中,8种人体必需氨基酸含量为31.70％,占氨基酸总量的40.85％.必需氨基酸的构成比例基本符合FAO/WHO的标准.三角鲂肌肉中限制性氨基酸主要为甲硫氨酸加胱氨酸,必需氨基酸指数为63.55,4种呈味氨基酸为氨基酸总量的32.81％;长春鳊肌肉中限制性氨基酸主要为色氨酸,必需氨基酸指数为66.81,4种呈味氨基酸为氨基酸总量的33.80％.脂肪酸中二十碳五烯酸(EPA)与二十二碳六烯酸(DHA)含量均较高,三角鲂为7.96％,长春鳊为3.11％.矿物元素比值合理.以上分析表明,三角鲂和长春鳊均为营养价值、经济价值都较高的优质鱼类,相比而言,三角鲂肌肉脂肪、脂肪酸含量和质量更优,而长春鳊肌肉在蛋白质、氨基酸组成与含量方面更优.     

Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues

The rate of glucose transport into cells is of fundamental importance in whole body homeostasis and adaptation to metabolic stresses, and this review examines the signalling mechanisms controlling this process. The events that mediate the action of insulin on glucose transport, which is by far the best characterized paradigm for glucose transport regulation, are discussed. There are several excellent reviews on various aspects of this subject, which are referred to while highlighting very recent developments in the field, including the recently described CAP pathway, and emerging mechanisms for feedback regulation of insulin signalling. The manner in which hormonal signalling is modulated by stimuli such as oxidative and osmotic stress is then discussed. The second major physiological event where glucose transport regulation is critical is the contraction of skeletal muscle, due to the large metabolic demands of this activity. The mechanism of this regulation is distinct from that initiated by insulin, and recent developments will be examined that have begun to clarify how contraction stimulates glucose transport in skeletal muscle, including the roles performed by AMP-activated protein kinase and nitric oxide synthase.     

糖原合酶激酶-3，一个信号通路的重要调控因子

糖原合酶激酶-3 (glycogen synthase kinase-3,GSK-3) 是一种多功能的丝氨酸／苏氨酸蛋白激酶,在蛋白质合成、信号传递、细胞增殖、细胞分化、神经功能、肿瘤形成及胚胎发育等众多细胞进程中均扮演重要的角色.GSK-3 能够使多种底物发生磷酸化,并参与胰岛素、Wnt及Hedgehog 等多个信号通路的调控. GSK-3抑制剂在信号通路中能有效地抑制病理情况下GSK-3活性的异常增高,达到治疗的目的.GSK-3的抑制剂将作为一种潜在的药物对治疗糖尿病、阿尔海默茨症、肿瘤等疾病发挥效用.     

Efecto de los movimientos explosivos y de impacto aplicados en piscina sobre la composición corporal,la fuerza y la densidad mineral ósea de mujeres mayores de 60 años

BackgroundOsteoporosis is characterised by loss of bone mass and deterioration of bone tissue microarchitecture that leads to fragility related to the risk of fractures. The aim of the study is to analyse the effects of a training program based on explosive movements and impact, assessed in a swimming pool, on body composition, explosive strength and bone mineral density in women over 60 years old.Material and methodsA total of 35 healthy physically active women (60 ± 4.19 years) were divided into a training pool group using multi jumps (JG) and a control group (CG). JG trained for 24 weeks, 3 times a week, an hour and a half per session. Body composition testing, explosive strength, and bone mineral density were assessed before and after the program.ResultsThere were differences in the explosive force (JG vs CG = P < .05 to .001) and the estimated power (JG vs CG = P < .05 to .002) between JG vs CG, with significant increases in JG. There were no significant differences in the percentage of fat and lean mass, bone mineral density lumbar and femoral between groups, although slightly significant increases in bone mineral density lumbar and femoral could be seen in JG after program implementation (JG pre-test vs JG post- test = P < .05).ConclusionsThe training program with impact and explosive movements assessed in a pool induces gains in muscle strength and power with slight adaptations in body mass index in women over 60 years.     

丙泊酚复合瑞芬太尼用于无肌松药气管插管的临床研究

目的:探讨丙泊酚复合瑞芬太尼用于无肌松药气管插管的最佳剂量,评估诱导期应用此种方法的有效性。方法:择期全麻的患者100例,ASAⅠ~Ⅱ级,随机分为三组。麻醉诱导为丙泊酚2 mg/kg,瑞芬太尼为2μg/kg(Ⅰ组)、3μg/kg(Ⅱ组)和4μg/kg(Ⅲ组),待两种药物达到药效高峰时行气管插管。观察诱导期和插管后1 min,3 min的血流动力学的变化情况,评估插管满意度。结果:各组的插管满意度如下:Ⅰ组54.2%(19/35)、Ⅱ组83.3%(25/30)、Ⅲ组97.1%(34/35),随着瑞芬太尼剂量的增加,气管插管满意度增高,气管插管操作时间缩短(P0.05)。在诱导过程中,三组患者的MAP和HR下降幅度均较显著(P0.05)。结论:丙泊酚复合瑞芬太尼用于无肌松药气管插管是可行的,与复合瑞芬太尼2μg/kg或3μg/kg相比,丙泊酚2 mg/kg复合瑞芬太尼4μg/kg能明显提供更好的气管插管条件,且插管操作时间明显缩短。     

Adaptations to isolated shoulder fatigue during simulated repetitive work. Part I: Fatigue

Upper extremity muscle fatigue is challenging to identify during industrial tasks and places changing demands on the shoulder complex that are not fully understood. The purpose of this investigation was to examine adaptation strategies in response to isolated anterior deltoid muscle fatigue while performing simulated repetitive work. Participants completed two blocks of simulated repetitive work separated by an anterior deltoid fatigue protocol; the first block had 20 work cycles and the post-fatigue block had 60 cycles. Each work cycle was 60 s in duration and included 4 tasks: handle pull, cap rotation, drill press and handle push. Surface EMG of 14 muscles and upper body kinematics were recorded. Immediately following fatigue, glenohumeral flexion strength was reduced, rating of perceived exertion scores increased and signs of muscle fatigue (increased EMG amplitude, decreased EMG frequency) were present in anterior and posterior deltoids, latissimus dorsi and serratus anterior. Along with other kinematic and muscle activity changes, scapular reorientation occurred in all of the simulated tasks and generally served to increase the width of the subacromial space. These findings suggest that immediately following fatigue people adapt by repositioning joints to maintain task performance and may also prioritize maintaining subacromial space width.     

Tendon reflex is suppressed during whole-body vibration

In this study we have investigated the effect of whole body vibration (WBV) on the tendon reflex (T-reflex) amplitude. Fifteen young adult healthy volunteer males were included in this study. Records of surface EMG of the right soleus muscle and accelerometer taped onto the right Achilles tendon were obtained while participant stood upright with the knees in extension, on the vibration platform. Tendon reflex was elicited before and during WBV. Subjects completed a set of WBV. Each WBV set consisted of six vibration sessions using different frequencies (25, 30, 35, 40, 45, 50 Hz) applied randomly. In each WBV session the Achilles tendon was tapped five times with a custom-made reflex hammer. The mean peak-to-peak (PP) amplitude of T-reflex was 1139.11 ± 498.99 µV before vibration. It decreased significantly during WBV (p < 0.0001). The maximum PP amplitude of T-reflex was 1333 ± 515 μV before vibration. It decreased significantly during WBV (p < 0.0001). No significant differences were obtained in the mean acceleration values of Achilles tendon with tapping between before and during vibration sessions. This study showed that T-reflex is suppressed during WBV. T-reflex suppression indicates that the spindle primary afferents must have been pre-synaptically inhibited during WBV similar to the findings in high frequency tendon vibration studies.