Journal: The Journal of physiology
Aerobic exercise such as running enhances adult hippocampal neurogenesis (AHN) in rodents. Little is known about the effects of high-intensity interval training (HIT) or of purely anaerobic resistance training on AHN. Here, compared to a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats. We find most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and - increase maximum running capacity. Our results confirm that sustained aerobic exercise is key in improving AHN.
We investigated the effects of adaptation to a ketogenic low-carbohydrate (CHO), high-fat diet (LCHF) during 3 wk of intensified training on metabolism and performance of world-class endurance athletes. We controlled three isoenergetic diets in elite race walkers: High CHO availability (8.6 g.kg(-) 1.d(-1) CHO, 2.1 g.kg(-) 1.d(-1) protein; 1.2 g.kg(-) 1.d(-1) fat) consumed before/during/after training (HCHO, n = 9): identical macronutrient intake, periodised within/between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (<50 g.d(-1) CHO; 78% energy as fat; 2.1 g.kg(-) 1.d(-1) protein; LCHF, n = 10). Post-intervention, VO2 peak during race walking increased in all groups (P < 0.001, 90%CI: [2.55 - 5.20%]). LCHF was associated with markedly increased rates of whole-body fat oxidation, attaining peak rates of 1.57 ± 0.32 g.min(-1) during 2 h of walking at ∼80%VO2 peak. However, LCHF also increased the oxygen (O2 ) cost of race walking at velocities relevant to real-life race performance: O2 uptake (expressed as % of new VO2peak ) at a speed approximating 20 km race pace was reduced in HCHO and PCHO (90%CI:[-7.047;-2.55] and [-5.18;-0.86], respectively, but was maintained at pre-intervention levels in LCHF. HCHO and PCHO groups improved times for 10 km race walk: 6.6% (90% CI: [4.1; 9.1%]) and 5.3% [3.4; 7.2%], with no improvement (-1.6% [-8.5; 5.3%] for the LCHF group. In contrast to training with diets providing chronic or periodised high-CHO availability, and despite a significant improvement in VO2peak , adaptation to the topical LCHF diet negated performance benefits in elite endurance athletes, in part, due to reduced exercise economy. This article is protected by copyright. All rights reserved.
This experiment assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty-eight, healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after six weeks of morning fasting (FAST; 0 kcal until 1200 h) or daily breakfast consumption (BFAST; ≥700 kcal before 1100 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin-stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were upregulated with FAST versus BFAST [1.14 (95%CI: 0.97 to 1.30) versus 0.80 (95%CI: 0.64 to 0.96), P = 0.007 and 1.75 (95%CI: 1.33 to 2.16) versus 1.09 (95%CI: 0.67 to 1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all P > 0.1). GLUT4, Akt protein content and insulin-stimulated Akt phosphorylation were unaffected by FAST versus BFAST in both lean and obese cohorts (all P > 0.1). Lower insulin-stimulated glucose uptake rates in obese versus lean individuals were eradicated when normalised to whole-body fat mass (P = 0.416). We conclude that morning fasting upregulates lipid turnover genes in SCAT of lean individuals. Secondly, altered SCAT insulin sensitivity with morning fasting is unlikely to be explained by signalling proximal to Akt. Finally, lower insulin-stimulated SCAT glucose uptake rates in obese individuals are proportional to whole-body fat mass, suggesting a compensatory downregulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726. This article is protected by copyright. All rights reserved.
Advanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth, and post-term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young), 5 (intermediate) months vs. 8 months (older) of age using infra-red video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3 month old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin-43 mRNA expression were reduced in myometrium from 8 month vs. 3 month old mice (P < 0.05, P < 0.01 respectively) in tandem with more frequent, but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, but there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8 month old mice provide a useful model of reproductive ageing. This study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women. This article is protected by copyright. All rights reserved.
Placebos have been found to affect the patient’s brain in a number of conditions, such as pain and motor disorders. For example, in Parkinson’s disease, a placebo treatment induces a release of dopamine in the striatum and changes the activity of neurons in both thalamic and subthalamic nuclei. The present study shows that placebo administration for the first time induces neither clinical nor neuronal improvement in Parkinson patients who undergo the implantation of electrodes for deep brain stimulation. However, this lack of placebo responsiveness can be turned into substantial placebo responses following previous exposure to repeated administrations of the anti-Parkinson agent apomorphine. As the number of apomorphine administrations increased from 1 through 4, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after 4 apomorphine exposures, placebo administration induced clinical responses that were as large as those to apomorphine, along with long-lasting neuronal changes. These clinical placebo responses following 4 apomorphine administrations were again elicited after a re-exposure to a placebo 24 hr post-surgery, but not after 48 hr. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo nonresponders can be turned into responders, with important implications in the clinical setting. This article is protected by copyright. All rights reserved.
Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by two hours recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca(2+) ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole FDB muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature. This article is protected by copyright. All rights reserved.
In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy, although their effects on the metabolism of the mother, in relation to feto-placental glucose utilization and growth, are unknown. In the present study, the consumption of an obesogenic HFHS diet compromised maternal glucose tolerance and insulin sensitivity in late pregnancy in association with dysregulated lipid and glucose handling by the dam. These maternal metabolic changes induced by HFHS feeding were related to altered feto-placental glucose metabolism and growth. A HFHS diet during pregnancy therefore causes maternal metabolic dysfunction with consequences for maternal nutrient allocation for fetal growth. These findings have implications for the health of women and their infants, who consume obesogenic diets during pregnancy.
We investigated functional, morphological and molecular adaptations to strength training exercise and cold water immersion (CWI) through two separate studies. In one study, 21 physically active men strength trained for 12 weeks (2 d⋅wk(-1) ), with either 10 min of CWI or active recovery (ACT) after each training session. Strength and muscle mass increased more in the ACT group than in the CWI group (P<0.05). Isokinetic work (19%), type II muscle fibre cross-sectional area (17%) and the number of myonuclei per fibre (26%) increased in the ACT group (all P<0.05) but not the CWI group. In another study, nine active men performed a bout of single-leg strength exercises on separate days, followed by CWI or ACT. Muscle biopsies were collected before and 2, 24 and 48 h after exercise. The number of satellite cells expressing neural cell adhesion molecule (NCAM) (10-30%) and paired box protein (Pax7)(20-50%) increased 24-48 h after exercise with ACT. The number of NCAM(+) satellitecells increased 48 h after exercise with CWI. NCAM(+) - and Pax7(+) -positivesatellite cell numbers were greater after ACT than after CWI (P<0.05). Phosphorylation of p70S6 kinase(Thr421/Ser424) increased after exercise in both conditions but was greater after ACT (P<0.05). These data suggest that CWI attenuates the acute changes in satellite cell numbers and activity of kinases that regulate muscle hypertrophy, which may translate to smaller long-term training gains in muscle strength and hypertrophy. The use of CWI as a regular post-exercise recovery strategy should be reconsidered. This article is protected by copyright. All rights reserved.
In this double-blind, randomized, controlled trial we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg vitamin C and 235 mg vitamin E daily or a placebo for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of 3-4 sessions per week (primarily running), divided into high intensity interval sessions (4-6x4-6 minutes; >90% of maximal heart rate (HRmax)) and steady state continuous sessions (30-60 minutes; 70-90% of HRmax). Maximal oxygen uptake (VO2max), submaximal running, and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. The vitamin C and E group increased their VO2max (8±5%) and performance in the 20 m shuttle test (10±11%) to the same degree as the placebo group (8±5% and 14±17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4; +59±97%) and cytosolic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha; +19±51%) increased in m. vastus lateralis in the placebo group, but not in the vitamin C and E group (COX4: -13±54%, PGC-1alpha: -13±29%; p≤0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group (p≤0.05, compared to the placebo group). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptions in the exercised muscles, and although this was not translated to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid Leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is “sensed” have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13C2]Leu and [2H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by A-V dilution). Orally consumed 3.42g free-acid (FA-HMB) HMB (providing 2.42g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42g Leu, stimulated MPS (HMB: +70% vs. Leu: +110 %). While HMB and Leu both increased anabolic signaling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e., p70S6K1 signaling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated MPB (-57 %) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.