Lactococcus lactis JCM 5805 (LC-Plasma) is a unique lactic acid bacteria (LAB) which activates plasmacytoid dendritic cells (pDC). We aimed to evaluate the effect of LC-Plasma on dendritic cell (DC) activity and subjective indices of upper respiratory tract infections (URTI) and fatigue in athletes under high intensity exercise. We conducted a randomized, placebo-controlled, double-blinded trial. Fifty-one male subjects belonging to a university sports club were randomized into placebo (n = 25) and LC-Plasma (n = 26) groups. Individuals ingested placebo capsules containing cornstarch or LC-Plasma capsules containing 100 billion cells of heat-killed LC-Plasma per day for 13 days. During the intervention period, subjects performed high intensity exercise according to their sports club training regime. Blood and saliva sampling were obtained at days 1 and 14, and physical conditions were recorded in a diary. We investigated expression of maturation markers on DCs, muscle damage and stress markers and used student’s t test adjusted by Bonferoni’s method for multiple comparison between groups. These data were presented as mean ± SD. We also investigated cumulative days of symptoms regarding infections and fatigue and used Chi-square test for comparison between groups. These data were presented as cumulative number. CD86 as maturation marker on pDC was significantly increased in the LC-Plasma group at day 14 (Placebo: 296 ± 70 vs. LC-Plasma: 365 ± 115; Mean Fluorescent Intensity; p = 0.013). Cumulative days of URTI were significantly lower in the LC-Plasma group (Placebo: URTI positive 56, URTI negative 256 vs. LC-Plasma: URTI positive 39, URTI negative 299; days; p = 0.028) and symptoms like sneeze or running nose were significantly lower in the LC-Plasma group (Placebo: Symptom positive 52, Symptom negative 258, vs. LC-Plasma: Symptom positive 36, Symptom negative 301; days; p = 0.032). Moreover, the cumulative days of fatigue were significantly fewer in the LC-Plasma group (Placebo: Symptom positive 128, Symptom negative 182, vs. LC-Plasma: Symptom positive 110, Symptom negative 225; days; p = 0.032). Markers of muscle damage and stress markers were not significantly different between groups. We consider that heat-killed LC-Plasma supplementation relieves morbidity and symptoms of URTI via activation of pDC and decreases fatigue accumulation during consecutive high intensity exercise in athletes. However, LC-Plasma ingestion did not affect markers of muscle damage and stress. UMIN-CTR, UMIN000020372 . Registered 28 December 2015.

Purpose: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. Methods: The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO_2max in 46 male Russian endurance athletes was determined using gas analysis system. Results: The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58–2.45; P = 1.7 × 10^–9). Furthermore, the HFE G allele was associated with high V̇O_2max in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036]. Conclusions: We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes.

Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10⁻⁵. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10⁻¹⁵) and with greater appendicular lean mass (p = 1.2 × 10⁻⁵), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.

Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver.

This study investigated the effects of long-term physical inactivity in adolescent on subsequent hindlimb unloading-induced muscle atrophy in rat soleus muscle. First, 3-wk-old male Wistar rats were assigned to an age-matched control (n = 6) or a physical inactivity (n = 8) group. Rats in the physical inactivity group were housed in narrow cages with approximately half the usual floor space for 8 wk to limit range of movement. Whole body energy consumption was measured, and the blood, organs, femoral bone, and hindlimb muscles were removed. We found that long-term physical inactivity did not affect the metabolic and physiological characteristics of growing rats. Then, fifty-six 3-wk-old male Wistar rats were assigned randomly into control (n = 28) and physical inactivity (n = 28) groups. After 8 wk, the rats in both groups underwent hindlimb unloading. The soleus muscles were removed before unloading (0 day), and 1, 3, and 7 days after unloading (n = 7 for each). Although the soleus muscle weight was significantly decreased after 7 days of hindlimb unloading in both groups, the decrease was drastic in the inactive group. A significant interaction between inactivity and unloading (P < 0.01) was observed according to the 4-hydroxynonenal-conjugated protein levels and the histone deacetylase 4 (HDAC4) and NF-κB protein levels. HDAC4 and NF-κB p65 protein levels in the physical inactivity group increased significantly 1 day after hindlimb unloading, along with the mRNA levels of their downstream targets myogenin and muscle RING finger protein 1 (MuRF1). Subsequent protein ubiquitination was upregulated by long-term physical inactivity (P < 0.05). NEW & NOTEWORTHY Long-term physical inactivity exacerbates hindlimb unloading-induced disuse muscle atrophy in young rat soleus muscles, possibly mediated by oxidative stress-induced protein ubiquitination via HDAC4- and NF-κB p65-induced MuRF1 mRNA upregulation.