Intermittent Fasting and High-Intensity Exercise Elicit Sexual-Dimorphic and Tissue-Specific Adaptations in Diet-Induced Obese Mice.

: The molecular adaptations that underpin body composition changes and health benefits of intermittent fasting (IF) and high-intensity interval training (HIIT) are unclear. The present study investigated these adaptations within the hypothalamus, white adipose and skeletal muscle tissue following 12 weeks of IF and/or HIIT in diet-induced obese mice. Mice (C57BL/6, 8-week-old, males/females) were fed high-fat (59%) and sugar (30%) water (HF/S) for 12 weeks followed by an additional 12 weeks of HF/S plus either IF, HIIT, combination (IF+HIIT) or HF/S only control (CON). Tissues were harvested at 12 and 24 weeks and analysed for various molecular markers. Hypothalamic NPY expression was significantly lower following IF+HIIT compared to CON in females. In adipose tissue, leptin expression was significantly lower following IF and IF+HIIT compared to CON in males and females. Males demonstrated increased markers of fat oxidation (HADH, FABP4) following IF+HIIT, whereas females demonstrated reduced markers of adipocyte differentiation/storage (CIDEC and FOXO1) following IF and/or IF+HIIT. In muscle, SIRT1, UCP3, PGC1α, and AS160 expression was significantly lower following IF compared to CON in males and/or females. This investigation suggests that males and females undertaking IF and HIIT may prevent weight gain via different mechanisms within the same tissue.

Adenylosuccinic acid therapy ameliorates murine Duchenne Muscular Dystrophy.

Arising from the ablation of the cytoskeletal protein dystrophin, Duchenne Muscular Dystrophy (DMD) is a debilitating and fatal skeletal muscle wasting disease underpinned by metabolic insufficiency. The inability to facilitate adequate energy production may impede calcium (Ca2+) buffering within, and the regenerative capacity of, dystrophic muscle. Therefore, increasing the metabogenic potential could represent an effective treatment avenue. The aim of our study was to determine the efficacy of adenylosuccinic acid (ASA), a purine nucleotide cycle metabolite, to stimulate metabolism and buffer skeletal muscle damage in the mdx mouse model of DMD. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were treated with ASA (3000 µg.mL-1) in drinking water. Following the 8-week treatment period, metabolism, mitochondrial density, viability and superoxide (O2-) production, as well as skeletal muscle histopathology, were assessed. ASA treatment significantly improved the histopathological features of murine DMD by reducing damage area, the number of centronucleated fibres, lipid accumulation, connective tissue infiltration and Ca2+ content of mdx tibialis anterior. These effects were independent of upregulated utrophin expression in the tibialis anterior. ASA treatment also increased mitochondrial viability in mdx flexor digitorum brevis fibres and concomitantly reduced O2- production, an effect that was also observed in cultured immortalised human DMD myoblasts. Our data indicates that ASA has a protective effect on mdx skeletal muscles.

Myoprotective Potential of Creatine Is Greater than Whey Protein after Chemically-Induced Damage in Rat Skeletal Muscle.

The myoprotective effects of creatine monohydrate (CR) and whey protein (WP) are equivocal, with the use of proxy measures of muscle damage making interpretation of their effectiveness limited. The purpose of the study was to determine the effects of CR and WP supplementation on muscle damage and recovery following controlled, chemically-induced muscle damage. Degeneration of the extensor digitorum longus (EDL) muscle was induced by bupivacaine in rats supplemented with either CR, WP, or standard rat chow (CON). At day 7 and 14 post-myotoxic injury, injured EDL muscles were surgically removed and tested for isometric contractile properties, followed by the contralateral, non-injured EDL muscle. At the completion of testing, muscles were snap-frozen in liquid nitrogen and stored for later analysis. Data were analyzed using analysis of variance. Creatine-supplemented muscles displayed a greater proportion of non-damaged (intact) fibers (p = 0.002) and larger cross-sectional areas of regenerating and non-damaged fibers (p = 0.024) compared to CON muscles at day 7 post-injury. At day 14 post-injury, CR-supplemented muscles generated higher absolute forces concomitant with greater contractile protein levels compared to CON (p = 0.001, p = 0.008) and WP-supplemented muscles (p = 0.003, p = 0.006). Creatine supplementation appears to offer an element of myoprotection which was not observed following whey protein supplementation.

No effect of acute beetroot juice ingestion on oxygen consumption, glucose kinetics, or skeletal muscle metabolism during submaximal exercise in males.

Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design. Two-and-a-half hours later, participants cycled for 60 min on an ergometer at 65% of V̇o2 peak. [6,6-(2)H]glucose was infused to determine glucose kinetics, blood samples obtained throughout exercise, and skeletal muscle biopsies that were obtained pre- and postexercise. Plasma nitrite [NO2 (-)] increased significantly (∼130%) with Beet, and this was attenuated in MW+Beet. Beet and Beet+MW had no significant effect on oxygen consumption, blood glucose, blood lactate, plasma nonesterified fatty acids, or plasma insulin during exercise. Beet and Beet+MW also had no significant effect on the increase in glucose disposal during exercise. In addition, Beet and Beet+MW had no significant effect on the decrease in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise. In conclusion, at the dose used, acute ingestion of beetroot juice had little effect on skeletal muscle metabolism during exercise.

Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal genetic muscle wasting disease with no current cure. A prominent, yet poorly treated feature of dystrophic muscle is the dysregulation of energy homeostasis which may be associated with intrinsic defects in key energy systems and promote muscle wasting. As such, supplementative nutriceuticals that target and augment the bioenergetical expansion of the metabolic pathways involved in cellular energy production have been widely investigated for their therapeutic efficacy in the treatment of DMD. We describe the metabolic nuances of dystrophin-deficient skeletal muscle and review the potential of various metabogenic and nutriceutical compounds to ameliorate the pathological and clinical progression of the disease.

The effect of ß-alanine and NaHCO3 co-ingestion on buffering capacity and exercise performance with high-intensity exercise in healthy males.

INTRODUCTION: ß-alanine (BAl) and NaHCO3 (SB) ingestion may provide performance benefits by enhancing concentrations of their respective physiochemical buffer counterparts, muscle carnosine and blood bicarbonate, counteracting acidosis during intense exercise. This study examined the effect of BAl and SB co-supplementation as an ergogenic strategy during high-intensity exercise. METHODS: Eight healthy males ingested either BAl (4.8 g day(-1) for 4 weeks, increased to 6.4 g day(-1) for 2 weeks) or placebo (Pl) (CaCO3) for 6 weeks, in a crossover design (6-week washout between supplements). After each chronic supplementation period participants performed two trials, each consisting of two intense exercise tests performed over consecutive days. Trials were separated by 1 week and consisted of a repeated sprint ability (RSA) test and cycling capacity test at 110 % Wmax (CCT110 %). Placebo (Pl) or SB (300 mg kgbw(-1)) was ingested prior to exercise in a crossover design to creating four supplement conditions (BAl-Pl, BAl-SB, Pl-Pl, Pl-SB). RESULTS: Carnosine increased in the gastrocnemius (n = 5) (p = 0.03) and soleus (n = 5) (p = 0.02) following BAl supplementation, and Pl-SB and BAl-SB ingestion elevated blood HCO3 (-) concentrations (p < 0.01). Although buffering capacity was elevated following both BAl and SB ingestion, performance improvement was only observed with BAl-Pl and BAl-SB increasing time to exhaustion of the CCT110 % test 14 and 16 %, respectively, compared to Pl-Pl (p < 0.01). CONCLUSION: Supplementation of BAl and SB elevated buffering potential by increasing muscle carnosine and blood bicarbonate levels, respectively. BAl ingestion improved performance during the CCT110 %, with no aggregating effect of SB supplementation (p > 0.05). Performance was not different between treatments during the RSA test.

Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males.

PURPOSE: The present study evaluated the effects of creatine monohydrate (CrM) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program. METHODS: In a double-blind, randomized trial, 20 males aged between 55 and 70 years were randomly assigned to consume either CrM-carbohydrate (CHO) [20 g days(-1) CrM + 5 g days(-1) CHO × 7 days, then 0.1 g kg(-1) CrM + 5 g CHO on training days (average dosage of ~8.8 g)] or placebo CHO (20 g days(-1) CHO × 7 days, then 5 g CHO on training days) while participating in a high intensity resistance training program [3 sets × 10 repetitions at 75% of 1 repetition maximum (1RM)], 3 days weeks(-1) for 12 weeks. Following the initial 7-day "loading" phase, participants were instructed to ingest their supplement within 60 min post-exercise. Body composition and muscle strength measurements, blood collection and vastus lateralis muscle biopsy were completed at 0, 4, 8 and 12 weeks of the supplement and resistance training program. RESULTS: A significant time effect was observed for 1RM bench press (p = 0.016), leg press (p = 0.012), body mass (p = 0.03), fat-free mass (p = 0.005) and total myofibrillar protein (p = 0.005). A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training (p = 0.08). No supplement interaction effects were observed. CONCLUSION: Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males.

A pilot study investigating the effect of Caralluma fimbriata extract on the risk factors of metabolic syndrome in overweight and obese subjects: a randomised controlled clinical trial.

OBJECTIVES: Central obesity is a key component of metabolic syndrome and it is often associated with other risk factors such as dyslipidemia, elevated plasma glucose levels and elevated blood pressure (BP). In this pilot study, the effect of Caralluma fimbriata (an edible succulent) extract in combination with controlled dietary intake and physical activity on these risk factors was assessed in overweight and obese Australian subjects. DESIGN: This was a randomised, double blind placebo controlled clinical trial. Forty-three adults aged 29-59 years were recruited. The eligibility criteria included a Body Mass Index (BMI) >25 kg/m(2), or a waist circumference >94 cm (male), >80 cm (female). Thirty-three participants completed the 12-week study at Victoria University Nutritional Therapy Clinic. Participants were randomly assigned into two groups. C. fimbriata extract and placebo were orally administered as 500 mg capsules twice daily (1 g/day) and dietary intake and exercise were monitored weekly. RESULTS: The results of thirty-three participants (experimental group, n = 17; placebo group n = 16) were analysed. The primary outcome measure was the decline in waist circumference. By week 9, the experimental group had lost 5.7 cm, compared to only 2.8 cm loss in the placebo group (Difference: -2.890; 95% CI; -5.802 to 0.023). Post intervention, the experimental group had lost 6.5 cm compared to 2.6 cm loss in the placebo group (Difference: -3.847; 95% CI; -7.466 to 0.228). Waist to hip ratio (WHR) also improved significantly after 12 weeks intervention in the experimental group, with a total reduction of 0.03 being recorded compared to 0.01 increase in the placebo group (Difference: -0.033; 95% CI; -0.064 to -0.002). There was also a significant decline in the palatability (visual appeal, smell, taste) of the test meal and sodium intake in the experimental group at week 12 (p < 0.05). In addition a significant reduction in body weight, BMI, hip circumference, systolic BP, HR, triglyceride levels, total fat and saturated fat intake within both groups was observed following the intervention period (p < 0.05). CONCLUSION: Supplementation with C. fimbriata extract whilst controlling overall dietary intake and physical activity may potentially play a role in curbing central obesity, the key component of metabolic syndrome. Controlling dietary intake and exercise improved body weight and favourably influenced the metabolic risk profile.

Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation.

Recent studies report that depletion and repletion of muscle taurine (Tau) to endogenous levels affects skeletal muscle contractility in vitro. In this study, muscle Tau content was raised above endogenous levels by supplementing male Sprague-Dawley rats with 2.5% (wt/vol) Tau in drinking water for 2 wk, after which extensor digitorum longus (EDL) muscles were examined for in vitro contractile properties, fatigue resistance, and recovery from fatigue after two different high-frequency stimulation bouts. Tau supplementation increased muscle Tau content by approximately 40% and isometric twitch force by 19%, shifted the force-frequency relationship upward and to the left, increased specific force by 4.2%, and increased muscle calsequestrin protein content by 49%. Force at the end of a 10-s (100 Hz) continuous tetanic stimulation was 6% greater than controls, while force at the end of the 3-min intermittent high-frequency stimulation bout was significantly higher than controls, with a 12% greater area under the force curve. For 1 h after the 10-s continuous stimulation, tetanic force in Tau-supplemented muscles remained relatively stable while control muscle force gradually deteriorated. After the 3-min intermittent bout, tetanic force continued to slowly recover over the next 1 h, while control muscle force again began to decline. Tau supplementation attenuated F(2)-isoprostane production (a sensitive indicator of reactive oxygen species-induced lipid peroxidation) during the 3-min intermittent stimulation bout. Finally, Tau transporter protein expression was not altered by the Tau supplementation. Our results demonstrate that raising Tau content above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle. Also, we demonstrate that raising Tau protects muscle function during high-frequency in vitro stimulation and the ensuing recovery period and helps reduce oxidative stress during prolonged stimulation.

Creatine supplementation reduces muscle inosine monophosphate during endurance exercise in humans.

INTRODUCTION: Creatine (Cr) supplementation has been shown to attenuate increases in plasma ammonia and hypoxanthine during intense endurance exercise lasting 1 h, suggesting that Cr supplementation may improve muscle energy balance (matching of ATP resynthesis to ATP demand) during such exercise. We hypothesized that Cr supplementation would improve muscle energy balance (as assessed by muscle inosine monophosphate (IMP) accumulation) during intense endurance exercise. METHODS: Seven well-trained men completed two experimental trials involving approximately 1 h of intense endurance exercise (cycling 45 min at 78+/-1% & OV0312;O2 peak followed by completion of 251+/-6 kJ as quickly as possible (performance ride)). Subjects ingested approximately 42 g.d dextrose for 5 d before the first experimental trial (CON), then approximately 21 g Cr monohydrate plus approximately 21 g.d dextrose for 5 d before the second experimental trial (CREAT). Trials were ordered because of the long washout time for Cr. Subjects were blinded to the order of the trials. RESULTS: Creatine supplementation significantly (P< 0.05) increased muscle total Cr (resting values: CREAT: 138.1+/-7.9; CON: 117.7+/- 6.5 mmol.kg dm). No difference was seen between treatments in any measured muscle or blood metabolite after the first 45 min of exercise. Despite the performance ride completion time being similar in the two treatments ( approximately 13.5 min, approximately 86% & OV0312;O2 peak), IMP at the end of the performance ride was significantly (P<0.05) lower in CREAT than in CON (CREAT: 1.2+/- 0.6; CON: 2.0+/- 0.7 mmol.kg dm). CONCLUSION: Raising muscle total Cr content before exercise appears to improve the ability of the muscle to maintain energy balance during intense aerobic exercise, but not during more moderate exercise intensities.