Carnosine, oxidative and carbonyl stress, antioxidants, and muscle fiber characteristics of quadriceps muscle of patients with COPD.

Oxidative/carbonyl stress is elevated in lower-limb muscles of patients with chronic obstructive pulmonary disease (COPD). Carnosine is a skeletal muscle antioxidant particularly present in fast-twitch fibers. The aims of the present study were to compare muscle carnosine, oxidative/carbonyl stress, antioxidants, and fiber characteristics between patients with COPD and healthy controls (HCs) and between patients after stratification for airflow limitation (mild/moderate vs. severe/very severe), as well as to investigate correlates of carnosine in patients with COPD. A vastus lateralis muscle biopsy was obtained from 40 patients with stable COPD and 20 age- and sex-matched HCs. Carnosine, oxidative/carbonyl stress, antioxidants, fiber characteristics, quadriceps strength and endurance (QE), V̇o2peak (incremental cycle test), and physical activity (PA) were determined. Patients with COPD had a similar carnosine concentration [4.16 mmol/kg wet weight (WW; SD = 1.93)] to HCs [4.64 mmol/kg WW (SD = 1.71)] and significantly higher percentage of fast-twitch fibers and lower QE, V̇o2peak, and PA versus HCs. Patients with severe/very severe COPD had a 31% lower carnosine concentration [3.24 mmol/kg WW (SD = 1.79); n = 15] versus patients with mild/moderate COPD [4.71 mmol/kg WW (SD = 1.83); n = 25; P = 0.02] and significantly lower V̇o2peak and PA versus patients with mild/moderate COPD. Carnosine correlated significantly with QE (rs = 0.427), V̇o2peak (rs = 0.334), PA (rs = 0.379), and lung function parameters in patients with COPD. In conclusion, despite having the highest proportion of fast-twitch fibers, patients with severe/very severe COPD displayed a 31% lower muscle carnosine concentration compared with patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.NEW & NOTEWORTHY Carnosine, particularly present in fast-twitch fibers, was investigated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD). Carnosine concentration was similar between patients with COPD and healthy controls but was 31% lower in patients with severe/very severe COPD, despite their high proportion of fast-twitch fibers, versus patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.

Acute preexercise supplementation of combined carnosine and anserine enhances initial maximal power of Wingate tests in humans.

Classic in vitro experiments (Severin's phenomenon) demonstrated that acute carnosine supplementation may potentiate muscle contractility. However, upon oral ingestion, carnosine is readily degraded in human plasma by the highly active serum carnosinase-1 (CN1). We developed a novel strategy to circumvent CN1 by preexercise ingestion of combined carnosine (CARN) and anserine (ANS), the methylated analog with similar biochemical properties but more resistant to CN1. First, in vitro hydrolysis was tested by adding carnosine and anserine to human plasma, alone or in combination. Second, five subjects were supplemented with 25 mg/kg anserine or 25 mg/kg of each anserine and carnosine to test in vivo bioavailability. Third, two double-blind, placebo-controlled, crossover studies investigated the effect of preexercise ANS + CARN (20 mg/kg body wt of each) supplementation on performance during a single all-out Wingate test following 6-min high-intensity cycling (study A) or three repeated Wingate tests (study B). In vitro experiments demonstrated slower degradation of anserine versus carnosine, which was further slowed by simultaneously adding carnosine. In vivo bioavailability of plasma anserine was more prominent [2.5-fold increased area under the curve (AUC)] when ANS + CARN versus ANS was ingested. Study A showed significantly higher (+6% ± 11%; P = 0.04) power in the first 5 s of the Wingate test following ANS + CARN (12.8 ± 2.4 W/kg) versus placebo (12.1 ± 2.2 W/kg). Study B demonstrated increased peak power (+3%) throughout three consecutive Wingate tests (ANS + CARN 10.5 ± 0.6 W/kg vs. placebo 10.2 ± 9.9 W/kg). These experiments reveal a novel acute nutritional method to effectively raise plasma anserine and carnosine by high-dose combined supplementation. This approach led to improved initial cycling power, revealing a new nutritional strategy to increase exercise performance.NEW & NOTEWORTHY Current results reveal that carnosine and anserine competitively bind to the highly active carnosinase enzyme in human plasma. Acute combined carnosine and anserine supplementation is therefore described as novel strategy to raise plasma anserine and carnosine. We report that indices of maximal exercise/muscle power during the initial stage of a Wingate test were significantly improved by preexercise 20-25mg/kg body wt anserine and carnosine supplementation, pointing toward a novel acute nutritional strategy to improve high-intensity exercise performance.

Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice.

PURPOSE: The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model. METHODS: We examined the effects of Orx either with or without testosterone (T) or estradiol (E2) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice. RESULTS: Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E2 administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E2, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx. CONCLUSIONS: The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.