Metabolic effects of α-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study.

Supplementation of health promoting nutraceuticals may be an effective adjunct strategy with other lifestyle and drug approaches to impede disease progression in prediabetic subjects. α-Lipoic acid, a naturally occurring short-chain fatty acid, has been extensively evaluated for its antioxidant and glycemic control properties but has rarely been investigated as a lipid-lowering strategy. We conducted a pilot study to examine the effects of α-lipoic acid supplementation on glycemic control and lipid profile in pre-diabetic, overweight/obese adults. The study was designed as a free-living, randomized, two-phase, placebo-controlled cross-over study with 12 pre-diabetic, dyslipidemic subjects. Eligible subjects completed two thirty-day phases (in random order) consisting of a placebo (600 mg cellulose per day) and α-lipoic acid treatment (600 mg day-1). Although no change (p < 0.05) in serum glucose was observed, α-lipoic acid-supplemented subjects demonstrated reduced fasting serum insulin (p = 0.04) and HOMA-IR (p = 0.07) compared with the placebo group. However, no change (p > 0.05) in serum lipids (including total cholesterol, LDL-C, HDL-C, triglycerides, LDL-C/HDL-C, and TC/HDL-C) were observed. Study results suggest that α-lipoic acid supplementation may be a useful strategy to improve insulin sensitivity in pre-diabetic subjects but is not effective in modulating serum lipids.

Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study.

Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men.

Metabolic response of different high-intensity aerobic interval exercise protocols.

Although high-intensity sprint interval training (SIT) employing the Wingate protocol results in significant physiological adaptations, it is conducted at supramaximal intensity and is potentially unsafe for sedentary middle-aged adults. We therefore evaluated the metabolic and cardiovascular response in healthy young individuals performing 4 high-intensity (~90% VO2max) aerobic interval training (HIT) protocols with similar total work output but different work-to-rest ratio. Eight young physically active subjects participated in 5 different bouts of exercise over a 3-week period. Protocol 1 consisted of 20-minute continuous exercise at approximately 70% of VO2max, whereas protocols 2-5 were interval based with a work-active rest duration (in seconds) of 30/30, 60/30, 90/30, and 60/60, respectively. Each interval protocol resulted in approximately 10 minutes of exercise at a workload corresponding to approximately 90% VO2max, but differed in the total rest duration. The 90/30 HIT protocol resulted in the highest VO2, HR, rating of perceived exertion, and blood lactate, whereas the 30/30 protocol resulted in the lowest of these parameters. The total caloric energy expenditure was lowest in the 90/30 and 60/30 protocols (~150 kcal), whereas the other 3 protocols did not differ (~195 kcal) from one another. The immediate postexercise blood pressure response was similar across all the protocols. These finding indicate that HIT performed at approximately 90% of VO2max is no more physiologically taxing than is steady-state exercise conducted at 70% VO2max, but the response during HIT is influenced by the work-to-rest ratio. This interval protocol may be used as an alternative approach to steady-state exercise training but with less time commitment.

Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury.

BACKGROUND: Some of the most serious consequences of normal ageing relate to its effects on skeletal muscle, particularly significant wasting and associated weakness, termed "sarcopenia". The underlying mechanisms of sarcopenia have yet to be elucidated completely but an altered muscle inflammatory response after injury is a likely contributing factor. In this study we investigated age-related changes in the expression of numerous inflammatory markers linked to successful muscle regeneration. METHODS: Right extensor digitorum longus (EDL) muscles from young (3 month), adult (12 month) and old (24 month) male F344 rats were injected with bupivacaine hydrochloride to cause complete muscle fibre degeneration, then excised 12, 24, 36, and 72 hours later (n = 5/age group/time point). We used qRT-PCR to quantify the mRNA expression levels of the inflammatory markers TNFα, IFNγ, IL1, IL18, IL6, and CD18 as well as regenerative markers MyoD and myogenin. RESULTS: Inflammatory markers were all increased significantly in all age groups after myotoxic injury. There was a trend for expression of inflammatory markers to be higher in uninjured muscles of old rats, especially at 72 hours post injury where the expression levels of several markers was significantly higher in old compared with young and adult rats. There was also a decrease in the expression of regenerative markers in old rats at 72 hours post injury. CONCLUSION: Our findings identify a prolonged inflammatory signature in injured muscles from old compared with young and adult rats together with a blunted expression of key markers of regeneration in muscles of old rats. Importantly, our findings identify potential targets for future therapeutic strategies for improving the regenerative capacity of skeletal muscle during ageing.

Episodic hypoxia exacerbates respiratory muscle dysfunction in DMD(mdx) mice.

Many patients with Duchenne muscular dystrophy (DMD) are eventually diagnosed with sleep-disordered breathing (SDB). SDB is associated with reduced ventilation, decreased arterial oxygen tension, and increased respiratory muscle recruitment during sleep, factors that could be especially detrimental to respiratory muscles in DMD. To assess whether SDB impacts dystrophin-deficient respiratory muscle function and fibrosis, diaphragm strength, and collagen content were evaluated in dystrophic mice (Dmd(mdx)) exposed to experimental SDB. Diurnal exposure to episodic hypoxia resulted in a 30% reduction in diaphragm strength without affecting collagen content. Episodic hypoxia secondary to SDB can exacerbate respiratory muscle dysfunction in DMD.

Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats.

Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O(2) levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats (P < 0.05). The pharyngeal pressure associated with airway collapse (P(crit)) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline P(crit) was more positive (more collapsible) in lean but not obese rats following 12 wk of IH (P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased P(crit)) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.

A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: impact of pirfenidone.

Skeletal muscles in mdx mice exhibit differential degrees of pathological changes and fibrosis. The purpose of this study was to examine differences in various indices of collagen metabolism in skeletal muscles with widely different functions and activity profiles in mdx mice, and to determine whether pirfenidone would attenuate the development of fibrosis. Mice in the pirfenidone group were orally fed pirfenidone (500 mg/kg) daily for 4 weeks. Marked differences were noted in hydroxyproline concentration between muscles, which could not be explained solely by the level of type I collagen and transforming growth factor-beta1 (TGF-beta1) mRNA. In normal mice, matrix metalloproteinase (MMP)-2 mRNA was significantly higher in the gastrocnemius than in the diaphragm or genioglossus muscles, suggesting that collagen degradation plays an important role in regulating collagen accretion in skeletal muscle. In mdx mice, the levels of both MMP-2 and MMP-9 mRNA were significantly elevated relative to control, although the response was muscle specific. Pirfenidone treatment resulted in a significant reduction in the level of hydroxyproline concentration across all muscles, although the effect was small. Results from this study reveal intrinsic dissimilarities in collagen metabolism between functionally different skeletal muscles. Moreover, the pharmacological use of pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy.

Respiratory muscle training improves swimming endurance in divers.

Respiratory muscles can fatigue during prolonged and maximal exercise, thus reducing performance. The respiratory system is challenged during underwater exercise due to increased hydrostatic pressure and breathing resistance. The purpose of this study was to determine if two different respiratory muscle training protocols enhance respiratory function and swimming performance in divers. Thirty male subjects (23.4 +/- 4.3 years) participated. They were randomized to a placebo (PRMT), endurance (ERMT), or resistance respiratory muscle training (RRMT) protocol. Training sessions were 30 min/day, 5 days/week, for 4 weeks. PRMT consisted of 10-s breath-holds once/minute, ERMT consisted of isocapnic hyperpnea, and RRMT consisted of a vital capacity maneuver against 50 cm H(2)O resistance every 30 s. The PRMT group had no significant changes in any measured variable. Underwater and surface endurance swim time to exhaustion significantly increased after RRMT (66%, P < 0.001; 33%, P = 0.003) and ERMT (26%, P = 0.038; 38%, P < 0.001). Breathing frequency (f (b)) during the underwater endurance swim decreased in RRMT (23%, P = 0.034) and tidal volume (V (T)) increased in both the RRMT (12%, P = 0.004) and ERMT (7%, P = 0.027) groups. Respiratory endurance increased in ERMT (216.7%) and RRMT (30.7%). Maximal inspiratory and expiratory pressures increased following RRMT (12%, P = 0.015, and 15%, P = 0.011, respectively). Results from this study indicate that respiratory muscle fatigue is a limiting factor for underwater swimming performance, and that targeted respiratory muscle training (RRMT > ERMT) improves respiratory muscle and underwater swimming performance.

Pentoxifylline fails to attenuate fibrosis in dystrophic (mdx) diaphragm muscle.

Fibrosis is a common pathological feature observed in muscle from patients with Duchenne muscular dystrophy and in mdx diaphragm. The purpose of this study was to determine whether pentoxifylline (PTX) treatment for 4 weeks (16 mg/kg/day) could significantly attenuate the process of fibrosis in diaphragm muscle from mdx mice. PTX treatment had no impact on in vitro diaphragm muscle contractile function. In addition, diaphragm muscle hydroxyproline concentration and the level of type I and III collagen and TGF-beta1 mRNA were unaffected by PTX treatment. These findings do not support the use of PTX as an antifibrotic drug for the treatment of muscular dystrophy.

Localization and early time course of TGF-beta 1 mRNA expression in dystrophic muscle.

Fibrosis is a common pathological feature observed in muscle from patients with Duchenne muscular dystrophy (DMD). In the dystrophic (mdx) mouse model of DMD, the diaphragm is more severely affected than other skeletal muscles. The level of transforming growth factor-beta1 (TGF-beta1), an inflammatory cytokine, is significantly elevated in mdx diaphragm. However, little is known about the onset of TGF-beta1 messenger ribonucleic acid (mRNA) expression, or which cells express the mRNA. In this study, we characterized the location and time course of expression of TGF-beta1 mRNA in diaphragm from mdx mice. TGF-beta1 mRNA was significantly elevated in mdx diaphragm at 6 and 9 but not 12 weeks of age, and these changes corresponded with changes in type I collagen mRNA and hydroxyproline concentration. Mononucleated cells localized to areas of fiber necrosis highly expressed the TGF-beta1 transcript in mdx diaphragm. Neutralization of TGF-beta1 by decorin administration resulted in a 40% reduction in the level of diaphragm muscle type I collagen mRNA. These findings support a role for TGF-beta1 during the early stages of fibrogenesis in dystrophic diaphragm muscle. Therapeutic interventions aimed at neutralizing this cytokine may be beneficial in slowing the development of fibrosis in DMD.