Octanoic Acid-Enrichment Diet Improves Endurance Capacity and Reprograms Mitochondrial Biogenesis in Skeletal Muscle of Mice

Background: Medium Chain Fatty Acids (MCFAs) are a dietary supplement that exhibit interesting properties, due to their smaller molecular size. The acute consumption of MCFAs is expected to enhance exercise performance. However, the short-term effects of MCFAs on endurance performance remains poorly understood. The aim of our study is to evaluate the octanoic acid (C8)-rich diet effect on endurance capacity, and to explore their molecular and cellular effects. Methods: C57BL/6J mice were fed with a chow diet (Control group) or an octanoic acid-rich diet (C8 diet) for 6 weeks. Spontaneous activity, submaximal and maximal exercise tests were carried out to characterize the exercise capacities of the mice. Beta-oxidation and mitochondrial biogenesis pathways were explored in skeletal muscle by RT-qPCR, Western Blot (Quadriceps) and histochemical staining (Gastrocnemius). Results: Mice fed with a C8-rich diet presented a higher spontaneous activity (p < 0.05) and endurance capacities (p < 0.05) than the control, but no effect on maximal effort was observed. They also presented changes in the skeletal muscle metabolic phenotype, with a higher number of the oxidative fibers, rich in mitochondria. At the molecular level, the C8-diet induced an AMPK activation (p < 0.05), associated with a significant increase in PGC1a and CS gene expression and protein levels. Conclusion: Our study provided evidence that C8-enrichment as a food supplementation improves endurance capacities and activates mitochondrial biogenesis pathways leading to higher skeletal muscle oxidative capacities.     

Apo-10'-lycopenoic acid, a lycopene metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice

Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 9',10'-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. In the present study, male ob/ob mice were fed a liquid high-fat diet (60% energy from fat) with ALA supplementation (ALA group, 240 μg?·?kg body weight(-1)?·?d(-1)) or without ALA supplementation as the control (C group) for 16 wk. Steatosis, SIRT1 expression and activity, genes involved in lipid metabolism, and ALA concentrations in the livers of mice were examined. The results showed that ALA supplementation resulted in a significant accumulation of ALA in the liver and markedly decreased the steatosis in the ALA group without altering body and liver weights compared to the C group. The mRNA and protein levels of hepatic SIRT1 were higher in the ALA group compared to the C group. SIRT1 activity also was higher in the ALA group, as indicated by the lower levels of acetylated forkhead box class O1 protein levels. In addition, the mRNA level of acetyl CoA carboxylase 1 was significantly lower in the ALA group than in the C group. Because SIRT1 plays a key role in lipid homeostasis, the present study suggests that the lycopene metabolite, ALA, protects against the development of steatosis in ob/ob mice by upregulating SIRT1 gene expression and activity.     

耐力运动及维生素E对大鼠心血管系统若干指标影响的实验研究

目的耐力运动具有促进心血管系统健康和增强抗氧化系统的重要作用,本研究探讨耐力训练和抗氧化剂干预对大鼠心血管系统若干指标的影响。方法48只SD大鼠随机分为六组,安静对照组Ⅰ(A,n=8)、安静对照组Ⅱ(B,n=8)、安静补VE对照组I(C,n=8)、安静补VE对照组Ⅱ(D,n=8)、耐力训练不补VE组(E,n=8)、耐力训练补VE组(F,n=8),进行4周耐力运动每周六天(60分钟/天)负重游泳。采用透射电镜观察心肌组织的超微结构,同时检测血清中的肿瘤坏死因子-α浓度和一氧化氮合成酶的活性。结果急性力竭运动的应激可引起大鼠心肌细胞形态特征结构变化,耐力运动及补充VE对大鼠血清NOS活性、TNF-α浓度的影响有差异。研究表明运动与抗氧化剂干预可以有效增强机体应激能力,可能与血液中TNF-α以及NOS活性的调节有关。结论耐力运动和维生素E干预对一次性大强度运动引起的心肌损伤具有保护作用。     

长期睡眠剥夺下调AMPK/SIRT1/PGC-1α通路引起小鼠脂代谢紊乱

目的探讨长期睡眠剥夺对小鼠肝组织腺苷酸激活蛋白激酶(adenosine 5’-monophosphateactivated protein kinase,AMPK)/沉默信息调节因子1(silent information regulation1,SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator-activated receptorγcoactivator 1α,PGC-1α)系统的影响。方法2月龄C57BL/6J小鼠16只随机分为睡眠剥夺组和正常对照组,睡眠剥夺组利用睡眠剥夺仪每天剥夺睡眠20 h,每周剥夺6 d,连续10周。正常对照组在相同实验条件下自由睡眠10周。每周测量一次体重,10周后进行小鼠体成分测定,并采集血液、肝脏和脂肪组织样本,检测血清褪黑素水平、肝组织AMPKα、SIRT1、PGC-1α及胆固醇调节元件结合蛋白1C(sterol regulatory element-binding protein 1C,SREBP-1C)蛋白表达水平,以及脂肪组织中脂肪合成关键酶脂肪酸合成酶(fatty acid synthase,FAS)、乙酰辅酶A羧化酶1(acetyl CoA carbosylase 1,ACC1)表达水平。结果建模结束后,睡眠剥夺组小鼠体重显著高于对照组(F=10.955,P=0.006),且从第6周末开始,睡眠剥夺组小鼠体重明显高于对照组(F=8.535,P=0.012),并且睡眠剥夺组小鼠体脂量[(14.58±1.70)%]高于对照组[(11.24±1.64)%](t=4.007,P=0.001),血清褪黑素浓度[(2.33±0.53)ng/ml]低于对照组[(2.87±0.23)ng/ml](t=2.643,P=0.019),AMPK通路中的AMPKα(t=7.134,P<0.001)、SIRT1(t=7.531,P<0.001)、PGC-1α(t=11.537,P<0.001)表达水平降低,AMPK/SIRT1/PGC-1α通路下调。而SREBP-1C表达水平升高,差异有统计学意义(t=-4.496,P=0.001)。同时睡眠剥夺小鼠脂肪组织中FAS(t=-4.375,P=0.001)、ACC1表达水平均升高(t=-4.072,P=0.001)。结论长期睡眠剥夺可致褪黑素受体介导的AMPK/SIRT1/PGC-1α通路抑制,并且脂肪合成相关基因表达增强,引起能量代谢特别是脂代谢稳态失调和体脂增加。     

Impact of Dietary Modifications on Plasma Sirtuins 1, 3 and 5 in Older Overweight Individuals Undergoing 12-Weeks of Circuit Training

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that regulate numerous pathways such as mitochondrial energy metabolism in the human body. Lower levels of these enzymes were linked to diseases such as diabetes mellitus and were also described as a result of aging. Sirtuins were previously shown to be under the control of exercise and diet, which are modifiable lifestyle factors. In this study, we analyzed SIRT1, SIRT3 and SIRT5 in blood from a subset of healthy elderly participants who took part in a 12-week randomized, controlled trial during which they performed, twice-weekly, resistance and aerobic training only (EX), the exercise routine combined with dietary counseling in accordance with the guidelines of the German Nutrition Society (EXDC), the exercise routine combined with intake of 2 g/day oil from Calanus finmarchicus (EXCO), or received no treatment and served as the control group (CON). In all study groups performing exercise, a significant increase in activities of SIRT1 (EX: +0.15 U/mg (+0.56/−[−0.16]), EXDC: +0.25 U/mg (+0.52/−0.06), EXCO: +0.40 U/mg (+0.88/−[−0.12])) and SIRT3 (EX: +0.80 U/mg (+3.18/−0.05), EXDC: 0.95 U/mg (+3.88/−0.55), EXCO: 1.60 U/mg (+2.85/−0.70)) was detected. Group comparisons revealed that differences in SIRT1 activity in EXCO and EXDC differed significantly from CON (CON vs. EXCO, p = 0.003; CON vs. EXDC, p = 0.010). For SIRT3, increases in all three intervention groups were significantly different from CON (CON vs. EX, p = 0.007; CON vs. EXDC, p < 0.001, CON vs. EXCO, p = 0.004). In contrast, differences in SIRT5-activities were less pronounced. Altogether, the analyses showed that the activity of SIRT1 and SIRT3 increased in response to the exercise intervention and that this increase may potentially be enhanced by additional dietary modifications.     

Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway

BACKGROUND/OBJECTIVESOligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined.MATERIALS/METHODSIn this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans.RESULTSOligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae.CONCLUSIONSThese data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.     

(-)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women

(-)-Hydroxycitric acid (HCA) is a competitive inhibitor of the enzyme ATPcitrate-lyase, which inhibits lipogenesis in the body. Moreover, HCA increases endurance exercise performance in trained mice and athletes. However, had not been investigated in untrained animals and humans. Therefore, we investigated the effects of short-term HCA ingestion on endurance exercise performance and fat metabolism in untrained women. In two experiments designed as a double-blind crossover test, six subjects ingested 250 mg of HCA or placebo (same amount of dextrin) via capsule for 5 d and then participated in cycle ergometer exercise. They cycled at 40% VO2max for 1 h and then the exercise intensity was increased to 60% VO2max until exhaustion on day 5 of each experiment. HCA tended to decrease the respiratory exchange ratio (RER) and carbohydrate oxidation during 1 h of exercise. In addition, exercise time to exhaustion was significantly enhanced (p<0.05). These results suggest that HCA increases fat metabolism, which may be associated with a decrease in glycogen utilization during the same intensity exercise and enhanced exercise performance.     

耐力运动及维生素E对大鼠心血管系统若干指标影响的实验研究

目的耐力运动具有促进心血管系统健康和增强抗氧化系统的重要作用,本研究探讨耐力训练和抗氧化剂干预对大鼠心血管系统若干指标的影响。方法48只SD大鼠随机分为六组,安静对照组Ⅰ（A,n=8）、安静对照组Ⅱ（B,n=8）、安静补VE对照组Ⅰ（C,n=8）、安静补VE对照组II（D,n=8）、耐力训练不补VE组（E,n=8）、耐力训练补VE组（F,n=8）,进行4周耐力运动每周六天（60分钟／天）负重游泳。采用透射电镜观察心肌组织的超微结构,同时检测血清中的肿瘤坏死因子-α浓度和一氧化氮合成酶的活性。结果急性力竭运动的应激可引起大鼠心肌细胞形态特征结构变化,耐力运动及补充VE对大鼠血清NOS活性、TNF—α浓度的影响有差异。研究表明运动与抗氧化剂干预可以有效增强机体应激能力,可能与血液中TNF—α以及NOS活性的调节有关。结论耐力运动和维生素E干预对一次性大强度运动引起的心肌损伤具有保护作用。     

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice

BACKGROUND/OBJECTIVESThe effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODSThis study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed.RESULTSThe ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation.CONCLUSIONSThese results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.     

Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency

BACKGROUND: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). OBJECTIVE: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate oxidation, glycolytic carbohydrate metabolism, and exercise endurance time and energy state of muscle in CID patients. DESIGN: Four CID patients and 15 control subjects were infused with triacylglycerol (3.7 mg x kg(-1) x min(-1)) or glucose (10 mg x kg(-1) x min(-1)) during low-intensity leg exercise. Respiratory calorimetry was used to evaluate mitochondrial substrate oxidation. The concentration and rate of appearance of plasma lactate (from dilution of [1-(13)C]lactate) were used to evaluate glycolytic carbohydrate metabolism. (31)P magnetic resonance spectroscopy was used to determine ratios of phosphocreatine to inorganic o-phosphate in forearm muscle during exercise. RESULTS: In 3 patients, leg exercise endurance time was better during the triacylglycerol infusion than during the glucose infusion. In all 4 patients, whole-body oxygen consumption rates during exercise were higher during triacylglycerol infusion than during the glucose infusion. In 3 patients, the concentration and rate of appearance of plasma lactate were lower during triacylglycerol infusion than during the glucose infusion. Ratios of phosphocreatine to inorganic o-phosphate during exercise were not significantly different between the 2 infusion studies or between the patients and control subjects. CONCLUSIONS: Triacylglycerol infusion is associated with a greater oxidation of substrates, lower rates of appearance and concentrations of plasma lactate, and greater leg exercise endurance time in myopathic CID patients than is glucose infusion. The energy state of muscle during exercise, however, was not significantly different after infusion of triacylglycerol or glucose.     

Substrate utilization during exercise performed with and without glucose ingestion in female and male endurance trained athletes

Compared to males, females oxidize proportionately more fat and less carbohydrate during endurance exercise performed in the fasted state. This study was designed to test the hypothesis that there may also be gender differences in exogenous carbohydrate (CHOexo) oxidation during exercise. Healthy, young males (n = 7) and females (n = 7) each completed 2 exercise trials (90 min cycle ergometry at 60% VO2peak), 1 week apart. Females were eumenorrheic and were tested in the midfollicular phase of their menstrual cycle. Subjects drank intermittently either 8% CHOexo (1 g glucose x kg x h(-1)) enriched with U-13C glucose or an artificially sweetened placebo during the trial. Whole-body substrate oxidation was determined from RER, urinary urea excretion, and the ratio of 13C:12C in expired gas during the final 60 min of exercise. During the placebo trial, fat oxidation was higher in females then in males (0.42 +/- 0.07 vs 0.32 +/- 0.09 g.min(-1).kg LBM(-1) x 10(2)) at 30 min of exercise (p < .05). When averaged over the final 60 min of exercise, the relative proportions of fat, total carbohydrate, and protein were all similar between groups. During CHOexo ingestion, both the ratio of 13C:12C in expired gas (p < .05) and the proportion of energy derived from CHOexo relative to LBM (p < .05) were higher in females compared to males at 75- and 90-min exercise. When averaged over the final 60 min of exercise, the percentage of CHOexo to the total energy contribution tended to be higher in females (14.3 +/- 1.2%) than in males (11.2 +/- 1.2%; p = .05). Compared to males, females may oxidize a greater relative proportion of CHOexo during endurance exercise which, in turn, may spare more endogenous fuel. Based on these observations, ingested carbohydrate may be a particularly beneficial source of fuel during endurance exercise for females.     

麦冬水提物对运动小鼠耐力的影响

目的研究麦冬水提物对运动小鼠耐力作用的影响。方法通过小鼠负重游泳试验、爬杆试验、转棒试验及疲劳仪试验,研究25、50、150 mg/kg BW d各剂量组对运动小鼠耐力的影响。结果与阴性对照组比较,麦冬水提物高剂量组和中剂量组均能明显延长小鼠负重游泳时间,差异有统计学意义(F值分别为22.335和10.391,均P<0.01);麦冬水提物的高、中剂量组也能使小鼠爬杆时间、转棒时间、致疲劳不动时的时间及奔跑距离明显延长,差异有统计学意义(均P<0.05)。结论麦冬水提物可提高运动小鼠的耐力,有明显的抗运动疲劳作用。     

Elevation of blood NAD level after moderate exercise in young women and mice

We previously reported that the blood NAD levels are decreased by severe exercise, and administration of nicotinamide, a precursor of NAD, improves the endurance capacity of mice. In the present study, we determined whether moderate exercise changes the blood NAD levels in humans and mice. College female students exercised moderately with bike-ergometers. The blood NAD levels elevated after moderate exercise. Mice were forced to swim in a running water pool for 5 min as a moderate exercise, 15 min as a strong exercise, and until exhaustion as a severe exercise (average swimming time was 28.7 min). A 5 min swim gave a result similar to that of moderate exercise by human subjects. However, the blood NAD levels decreased after all-out exercise. The changes in whole blood tryptophan (a precursor of pyridine nucleotides) levels were similar to that in NAD. The glucose levels in whole blood and the non-esterified fatty acid levels in serum decreased according to exercising time. These data are the first demonstration of moderate exercise raising the blood NAD levels in human and mice. Elevation of the blood NAD levels may reflect changes in niacin metabolism that occur in response to exercise.