Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity

The gut microbiota is considered a relevant factor in obesity and associated metabolic diseases, for which postmenopausal women are particularly at risk. Increasing physical activity has been recognized as an efficacious approach to prevent or treat obesity, yet the impact of physical activity on the microbiota remains under-investigated. We examined the impacts of voluntary exercise on host metabolism and gut microbiota in ovariectomized (OVX) high capacity (HCR) and low capacity running (LCR) rats. HCR and LCR rats (age = 27wk) were OVX and fed a high-fat diet (45% kcal fat) ad libitum and housed in cages equipped with (exercise, EX) or without (sedentary, SED) running wheels for 11wk (n = 7-8/group). We hypothesized that increased physical activity would hinder weight gain, increase metabolic health and shift the microbiota of LCR rats, resulting in populations more similar to that of HCR rats. Animals were compared for characteristic metabolic parameters including body composition, lipid profile and energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise decreased body and fat mass, and normalized fasting NEFA concentrations of LCR rats, despite only running one-third the distance of HCR rats. Exercise, however, increased food intake, weight gain and fat mass of HCR rats. Exercise clustered the gut microbial community of LCR rats, which separated them from the other groups. Assessments of specific taxa revealed significant (p<0.05) line by exercise interactions including shifts in the abundances of Firmicutes, Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae family was higher (p = 0.026) in HCR than LCR rats, and positively correlated (p<0.05) with food intake, body weight and running distance. These findings demonstrate that exercise differentially impacts host metabolism and gut microbial communities of female HCR and LCR rats without ovarian function.     

Rats Bred for Low Aerobic Capacity Become Promptly Fatigued and Have Slow Metabolic Recovery after Stimulated,Maximal Muscle Contractions

AIM

Muscular fatigue is a complex phenomenon affected by muscle fiber type and several metabolic and ionic changes within myocytes. Mitochondria are the main determinants of muscle oxidative capacity which is also one determinant of muscle fatigability. By measuring the concentrations of intracellular stores of high-energy phosphates it is possible to estimate the energy production efficiency and metabolic recovery of the muscle. Low intrinsic aerobic capacity is known to be associated with reduced mitochondrial function. Whether low intrinsic aerobic capacity also results in slower metabolic recovery of skeletal muscle is not known. Here we studied the influence of intrinsic aerobic capacity on in vivo muscle metabolism during maximal, fatiguing electrical stimulation.

METHODS

Animal subjects were genetically heterogeneous rats selectively bred to differ for non–trained treadmill running endurance, low capacity runners (LCRs) and high capacity runners (HCRs) (n = 15–19). We measured the concentrations of major phosphorus compounds and force parameters in a contracting triceps surae muscle complex using ³¹P-Magnetic resonance spectroscopy (³¹P-MRS) combined with muscle force measurement from repeated isometric twitches.

RESULTS

Our results demonstrated that phosphocreatine re-synthesis after maximal muscle stimulation was significantly slower in LCRs (p<0.05). LCR rats also became promptly fatigued and maintained the intramuscular pH poorly compared to HCRs. Half relaxation time (HRT) of the triceps surae was significantly longer in LCRs throughout the stimulation protocol (p≤0.05) and maximal rate of torque development (MRTD) was significantly lower in LCRs compared to HCRs from 2 min 30 s onwards (p≤0.05).

CONCLUSION

We observed that LCRs are more sensitive to fatigue and have slower metabolic recovery compared to HCRs after maximal muscle contractions. These new findings are associated with reduced running capacity and with previously found lower mitochondrial content, increased body mass and higher complex disease risk of LCRs.     

Sweet Success,Bitter Defeat: A Taste Phenotype Predicts Social Status in Selectively Bred Rats

For social omnivores such as rats and humans, taste is far more than a chemical sense activated by food. By virtue of evolutionary and epigenetic elaboration, taste is associated with negative affect, stress vulnerability, responses to psychoactive substances, pain, and social judgment. A crucial gap in this literature, which spans behavior genetics, affective and social neuroscience, and embodied cognition, concerns links between taste and social behavior in rats. Here we show that rats selectively bred for low saccharin intake are subordinate to high-saccharin-consuming rats when they compete in weight-matched dyads for food, a task used to model depression. Statistical and experimental controls suggest that differential resource utilization within dyads is not an artifact of individual-level processes such as apparatus habituation or ingestive motivation. Tail skin temperature measurements showed that LoS rats display larger hyperthermic responses to social interaction after status is established, evidence linking taste, social stress, autonomic reactivity, and depression-like symptoms. Based on regression using early- and late-competition predictors to predict dyadic disparity in final competition scores, we tentatively suggest that HiS rats emerge as dominant both because of an “early surge” on their part and because LoS acquiesce later. These findings should invigorate the comparative study of individual differences in social status and its relationship to mental and physical health.     

Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats

Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by alcohol-preferring P rats as a result of chronic voluntary exposure may have favorable vs. detrimental effects on lipid profiles in this genetic line, consistent with data supporting beneficial cardioprotective and neuroprotective effects of moderate ethanol consumption.     

Chronic Hyperhomocysteinemia Increases Inflammatory Markers in Hippocampus and Serum of Rats

This study investigated the effects of chronic homocysteine administration on some parameters of inflammation, such as cytokines (TNF-α, IL-1β and IL-6), chemokine CCL(2) (MCP-1), nitrite and prostaglandin E(2) levels, as well as on immunocontent of NF-κB/p65 subunit in hippocampus and/or serum of rats. Since acetylcholinesterase has been associated with inflammation, we also evaluated the effect of homocysteine on this enzyme activity in hippocampus of rats. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 μmol/g body weight) or saline (control) from the 6th to the 28th days-of-age. One or 12 h after the last injection, rats were euthanized and hippocampus and serum were used. Results showed that chronic hyperhomocysteinemia significantly increased pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), chemokine CCL(2) (MCP-1) and prostaglandin E(2) in hippocampus and serum of rats at 1 and 12 h after the last injection of homocysteine. Nitrite levels increased in hippocampus, but decreased in serum at 1 h after chronic hyperhomocysteinemia. Acetylcholinesterase activity and immunocontent of citoplasmic and nuclear NF-κB/p65 subunit were increased in hippocampus of rats subjected to hyperhomocysteinemia at 1 h, but did not alter at 12 h after the last injection of homocysteine. According to our results, chronic hyperhomocysteinemia increases inflammatory parameters, suggesting that this process might be associated, at least in part, with the cerebrovascular and vascular dysfunctions characteristic of some homocystinuric patients.     

Long-Term Oral Feeding of Lutein-Fortified Milk Increases Voluntary Running Distance in Rats

To evaluate the effects of lutein-fortified milk administration on running exercise, a voluntary wheel-running model was performed in rats. Four-week-old F344 rats were administered test milk (10 mL/kg) daily following a 4-h fasting period, and their running distances were measured each day for a 9-week period. Total weekly running distance significantly increased from the sixth week until the end of the test period in lutein-supplemented rats (lutein-fortified milk administered) compared with control rats (vehicle administered). This increase was not apparent in rats administered lutein alone. In the lutein-fortified-milk exercise group compared with the sedentary control group, carnitine palitroyltransferase 1 (CPT-1), total AMP-activated protein kinase (tAMPK), and phosphorylated AMP-activated protein kinase (pAMPK) contents were significantly increased in the gastrocnemius muscle, with a concomitant decrease in triglyceride and total cholesterol levels in the blood and liver. Furthermore, the lutein level in blood of lutein-administered rats significantly decreased with exercise. These results suggest that lutein-fortified milk may enhance the effect of exercise by effective utilization of lipids when combined with voluntary running.     

Voluntary Running Exercise Alters Microbiota Composition and Increases n-Butyrate Concentration in the Rat Cecum

The effects of voluntary wheel-running exercise on cecal microbiota and short-chain fatty acid production were investigated in rats. The microbiota composition was notably different between the exercised and sedentary rats. Furthermore, the exercised rats showed a significantly higher n-butyrate concentration than the sedentary rats. This alteration of the cecal microbial environment may contribute to the beneficial effect of exercise on gastrointestinal disorders.     

Running Exercise Improves Metabolic Abnormalities and Fat Accumulation in Sucrose-Induced Insulin-Resistant Rats

NARA, MAKOTO, MASAKI TAKAHASHI, TSUGIYASU KANDA, YOUNOSUKE SHIMOMURA, ISAO KOBAYASHI. Running exercise improves metabolic abnormalities and fat accumulation in sucrose-induced insulin-resistant rats. Insulin resistance and hyperinsulinemia are observed in rats fed a high sucrose diet. Insulin resistance is thought to be related to abnormal fat distribution. We previously reported the metabolic characteristics and the fat distribution in rats with sucrose-induced insulin resistance. This study was designed to examine the effects of exercise in these rats. The rats were divided into three groups: those receiving a starch-based diet (control), those receiving a high-sucrose diet (sucrose fed), and those receiving a high-sucrose diet and wheel-running exercise (exercised). Animals were killed after 4 weeks or 12 weeks. After 4 weeks, the three groups did not differ with respect to gain in adipose tissues. The portal vein (PV) insulin concentration was significantly increased in the sucrose-fed and the exercised rats compared with the control rats. The inferior vena cava (IVC) glucose concentration and the PV free fatty acid (FFA) were significantly lower in the exercised rats than in the sucrose-fed rats. After 12 weeks, the exercised rats had significantly lower mesenteric fat (MS) and subcutaneous fat (SC) and a lower MS:SC ratio than the sucrose-fed rats. The glucose levels in IVC, PV, and FFA in PV were significantly reduced in the exercised rats as compared with the sucrose-fed rats. These findings suggest that long-term exercise improves insulin resistance by reducing the accumulation of MS as well as SC. It is also suggested that short-term exercise improves glucose metabolism without change of fat accumulation.     

低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响

Nrf2可调节多种抗氧化酶的表达,Nrf2的缺失可能影响机体的运动能力,而低氧可提高机体的抗氧化能力并改善运动能力。为了考察低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响,本研究分别在常氧和低氧环境(12%氧浓度)中对野生型大鼠和Nrf2敲除大鼠进行4周的跑台运动。研究显示,低氧运动可提高野生型大鼠的跑台运动力竭时间,Nrf2敲除可缩短大鼠的力竭时间;低氧运动可上调大鼠的Nrf2 m RNA表达量;Nrf2敲除明显抑制HIF-1α蛋白表达,而低氧运动可上调野生型和Nrf2敲除大鼠的HIF-1α蛋白表达;Nrf2敲除大鼠的骨骼肌ROS水平明显升高,并且低氧均可降低野生型和Nrf2敲除大鼠骨骼肌ROS水平。低氧运动可上调Nrf2敲除大鼠的CAT和GSH-PX蛋白表达。苏木精和伊红(HE)染色显示,Nrf2敲除大鼠在力竭跑台运动完成后出现更严重的骨骼肌病理改变,而低氧运动可减轻骨骼肌损伤。本研究认为,Nrf2敲除导致了大鼠骨骼肌中抗氧化酶的抑制及ROS的过量累积,从而造成了骨骼肌损伤并降低了运动能力。此外,低氧可通过上调Nrf2的表达,进而激活HIF-1α及抗氧化酶活性,从而提高运动能力,并防止骨骼肌损伤。     

Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.     

红景天对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响

本文以大强度耐力训练大鼠为模型,对红景天对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响进行了研究。试验中分别以0.58、1.16、4.48 g.kg-1/d的剂量给大鼠灌胃42 d,并进行负重游泳实验、血清睾酮等生化指标测定。结果显示,红景天各剂组力竭游泳时间长于运动对照组(T组)(P<0.01);血清睾酮高于T组(P<0.01),血清皮质酮低于T组(P<0.05);各组间血清睾酮与皮质酮比值变化与睾酮变化较为一致;肝糖原(P<0.05)、肌糖原(P<0.01)高于T组;血清尿素氮低于T组(P<0.05);血红蛋白高于T组(P<0.05)。从而表明补充红景天可以减轻大鼠血睾酮、皮质酮受高强度运动量的影响,维持在正常生理水平;促进蛋白质合成,抑制氨基酸和蛋白质分解,提高血红蛋白含量和糖原的储备,增强抗疲劳能力,具有多靶点、多途径的显著特点。     

Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5–15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15–51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines.     

Decreased Histamine-Stimulated Phosphoinositide Hydrolysis in the Cerebral Cortex of a Rat Line Selectively Bred for High Alcohol Preference

This study sheds light on the comparative analysis of agonist-stimulated phosphoinositide (PI) hydrolysis in the cerebral cortex of alcohol-naive rats from established lines selectively bred for low alcohol preference (LAP) and high alcohol preference (HAP). The effect of histamine (1.0 mM), but neither norepinephrine (0.1 mM) nor carbachol (0.5 mM), on PI hydrolysis was significantly reduced in HAP rats (0.4 +/- 5.0 fmol/mg protein [3H]inositol phosphates formed over basal) compared with LAP rats (25.5 +/- 10.0 fmol/mg protein). The contents of monoamines (dopamine, norepinephrine, and serotonin) and histamine in the cerebral cortex did not significantly differ between LAP and HAP rats, nor did the contents of their metabolites, except 3-methoxy-4-hydroxyphenylglycol (one of the metabolites of norepinephrine) and N(tau)-methylhistamine, which was not detected in our system. The histamine stimulatory effect was unchanged in the cerebral cortex of an intact Wistar rat that was treated with intraperitoneal injection of alcohol (1.0 g/kg once per day for 14 days). The results of the current study indicate that the decrease in the histamine effect on PI hydrolysis in HAP rats might be attributed to that particular rat line.     

Three Minutes of All-Out Intermittent Exercise per Week Increases Skeletal Muscle Oxidative Capacity and Improves Cardiometabolic Health

We investigated whether a training protocol that involved 3 min of intense intermittent exercise per week — within a total training time commitment of 30 min including warm up and cool down — could increase skeletal muscle oxidative capacity and markers of health status. Overweight/obese but otherwise healthy men and women (n = 7 each; age  = 29±9 y; BMI  = 29.8±2.7 kg/m²) performed 18 training sessions over 6 wk on a cycle ergometer. Each session began with a 2 min warm-up at 50 W, followed by 3×20 s “all-out” sprints against 5.0% body mass (mean power output: ∼450–500 W) interspersed with 2 min of recovery at 50 W, followed by a 3 min cool-down at 50 W. Peak oxygen uptake increased by 12% after training (32.6±4.5 vs. 29.1±4.2 ml/kg/min) and resting mean arterial pressure decreased by 7% (78±10 vs. 83±10 mmHg), with no difference between groups (both p<0.01, main effects for time). Skeletal muscle biopsy samples obtained before and 72 h after training revealed increased maximal activity of citrate synthase and protein content of cytochrome oxidase 4 (p<0.01, main effect), while the maximal activity of β-hydroxy acyl CoA dehydrogenase increased in men only (p<0.05). Continuous glucose monitoring measured under standard dietary conditions before and 48–72 h following training revealed lower 24 h average blood glucose concentration in men following training (5.4±0.6 vs. 5.9±0.5 mmol/L, p<0.05), but not women (5.5±0.4 vs. 5.5±0.6 mmol/L). This was associated with a greater increase in GLUT4 protein content in men compared to women (138% vs. 23%, p<0.05). Short-term interval training using a 10 min protocol that involved only 1 min of hard exercise, 3x/wk, stimulated physiological changes linked to improved health in overweight adults. Despite the small sample size, potential sex-specific adaptations were apparent that warrant further investigation.     

Running for Exercise Mitigates Age-Related Deterioration of Walking Economy

Introduction

Impaired walking performance is a key predictor of morbidity among older adults. A distinctive characteristic of impaired walking performance among older adults is a greater metabolic cost (worse economy) compared to young adults. However, older adults who consistently run have been shown to retain a similar running economy as young runners. Unfortunately, those running studies did not measure the metabolic cost of walking. Thus, it is unclear if running exercise can prevent the deterioration of walking economy.

Purpose

To determine if and how regular walking vs. running exercise affects the economy of locomotion in older adults.

Methods

15 older adults (69±3 years) who walk ≥30 min, 3x/week for exercise, “walkers” and 15 older adults (69±5 years) who run ≥30 min, 3x/week, “runners” walked on a force-instrumented treadmill at three speeds (0.75, 1.25, and 1.75 m/s). We determined walking economy using expired gas analysis and walking mechanics via ground reaction forces during the last 2 minutes of each 5 minute trial. We compared walking economy between the two groups and to non-aerobically trained young and older adults from a prior study.

Results

Older runners had a 7–10% better walking economy than older walkers over the range of speeds tested (p = .016) and had walking economy similar to young sedentary adults over a similar range of speeds (p = .237). We found no substantial biomechanical differences between older walkers and runners. In contrast to older runners, older walkers had similar walking economy as older sedentary adults (p = .461) and ∼26% worse walking economy than young adults (p<.0001).

Conclusion

Running mitigates the age-related deterioration of walking economy whereas walking for exercise appears to have minimal effect on the age-related deterioration in walking economy.     

菟丝子对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响

本文以大强度耐力训练大鼠为模型,对菟丝子对运动训练大鼠睾酮含量、物质代谢及抗运动疲劳能力的影响进行了研究.试验中分别以1.16、2.32、6.96 g.kg-1.d-1的剂量给大鼠灌胃42d,并进行负重游泳实验、血清睾酮等生化指标测定.结果显示,菟丝子各剂量组力竭游泳时间长于运动对照组(T组)(P＜0.01);血清睾酮高于T组(P＜0.01),血清皮质酮低于T组(P＜0.05);各组间血清睾酮与皮质酮比值变化与睾酮变化较为一致;肝糖原(P＜0.05)、肌糖原(P＜0.01)高于T组;血清尿素氮低于T组(P＜0.05);血红蛋白高于T组(P＜0.05).从而表明补充菟丝子可以减轻大鼠血睾酮、皮质酮受高强度运动量的影响,维持在正常生理水平;促进蛋白质合成,抑制氨基酸和蛋白质分解,提高血红蛋白含量和糖原的储备,增强抗疲劳能力,具有多靶点、多途径的显著特点.