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Concept: Anabolism


There is currently no evidence that the intervertebral discs (IVDs) can respond positively to exercise in humans. Some authors have argued that IVD metabolism in humans is too slow to respond anabolically to exercise within the human lifespan. Here we show that chronic running exercise in men and women is associated with better IVD composition (hydration and proteoglycan content) and with IVD hypertrophy. Via quantitative assessment of physical activity we further find that accelerations at fast walking and slow running (2 m/s), but not high-impact tasks, lower intensity walking or static positions, correlated to positive IVD characteristics. These findings represent the first evidence in humans that exercise can be beneficial for the IVD and provide support for the notion that specific exercise protocols may improve IVD material properties in the spine. We anticipate that our findings will be a starting point to better define exercise protocols and physical activity profiles for IVD anabolism in humans.

Concepts: Metabolism, Exercise, Vertebral column, Physical quantities, Intervertebral disc, Stretching, Anabolism, Catabolism


Reports concerning the effect of endurance exercise on the anabolic response to strength training have been contradictory. This study re-investigated this issue, focusing on training effects on indicators of protein synthesis and degradation. Two groups of male subjects performed 7 weeks of resistance exercise alone (R; n = 7) or in combination with preceding endurance exercise, including both continuous and interval cycling (ER; n = 9). Muscle biopsies were taken before and after the training period. Similar increases in leg-press 1 repetition maximum (30%; P<0.05) were observed in both groups, whereas maximal oxygen uptake was elevated (8%; P<0.05) only in the ER group. The ER training enlarged the areas of both type I and type II fibers, whereas the R protocol increased only the type II fibers. The mean fiber area increased by 28% (P<0.05) in the ER group, whereas no significant increase was observed in the R group. Moreover, expression of Akt and mTOR protein was enhanced in the ER group, whereas only the level of mTOR was elevated following R training. Training-induced alterations in the levels of both Akt and mTOR protein were correlated to changes in type I fiber area (r = 0.55-0.61, P<0.05), as well as mean fiber area (r = 0.55-0.61, P<0.05), reflecting the important role played by these proteins in connection with muscle hypertrophy. Both training regimes reduced the level of MAFbx protein (P<0.05) and tended to elevate that of MuRF-1. The present findings indicate that the larger hypertrophy observed in the ER group is due more to pronounced stimulation of anabolic rather than inhibition of catabolic processes.

Concepts: Protein, Metabolism, Exercise, Muscular system, Strength training, Exercise physiology, Anabolism, Muscle hypertrophy


While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

Concepts: Metabolism, Nutrition, Insulin, Obesity, Metabolic pathway, Dieting, Anabolism, Catabolism


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.

Concepts: Protein, Amino acid, Metabolism, Muscle, Actin, Myosin, Leucine, Anabolism


It is well established that regimented resistance training can promote increases in muscle hypertrophy. The prevailing body of research indicates that mechanical stress is the primary impetus for this adaptive response and studies show that mechanical stress alone can initiate anabolic signalling. Given the dominant role of mechanical stress in muscle growth, the question arises as to whether other factors may enhance the post-exercise hypertrophic response. Several researchers have proposed that exercise-induced metabolic stress may in fact confer such an anabolic effect and some have even suggested that metabolite accumulation may be more important than high force development in optimizing muscle growth. Metabolic stress pursuant to traditional resistance training manifests as a result of exercise that relies on anaerobic glycolysis for adenosine triphosphate production. This, in turn, causes the subsequent accumulation of metabolites, particularly lactate and H(+). Acute muscle hypoxia associated with such training methods may further heighten metabolic buildup. Therefore, the purpose of this paper will be to review the emerging body of research suggesting a role for exercise-induced metabolic stress in maximizing muscle development and present insights as to the potential mechanisms by which these hypertrophic adaptations may occur. These mechanisms include increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species and cell swelling. Recommendations are provided for potential areas of future research on the subject.

Concepts: Oxygen, Metabolism, Adenosine triphosphate, Oxidative phosphorylation, Force, Anabolic steroid, Anabolism, Muscle hypertrophy


Myostatin and activin A are structurally related secreted proteins that act to limit skeletal muscle growth. The cellular targets for myostatin and activin A in muscle and the role of satellite cells in mediating muscle hypertrophy induced by inhibition of this signaling pathway have not been fully elucidated. Here we show that myostatin/activin A inhibition can cause muscle hypertrophy in mice lacking either syndecan4 or Pax7, both of which are important for satellite cell function and development. Moreover, we show that muscle hypertrophy after pharmacological blockade of this pathway occurs without significant satellite cell proliferation and fusion to myofibers and without an increase in the number of myonuclei per myofiber. Finally, we show that genetic ablation of Acvr2b, which encodes a high-affinity receptor for myostatin and activin A specifically in myofibers is sufficient to induce muscle hypertrophy. All of these findings are consistent with satellite cells playing little or no role in myostatin/activin A signaling in vivo and render support that inhibition of this signaling pathway can be an effective therapeutic approach for increasing muscle growth even in disease settings characterized by satellite cell dysfunction.

Concepts: Protein, Gene, Signal transduction, Cell biology, Satellite cell, Muscular system, Anabolism, Muscle hypertrophy


Growth regulation in adult Atlantic salmon (1.6 kg) was investigated during 45 days in seawater at 13, 15, 17, and 19 °C. We focused on feed intake, nutrient uptake, nutrient utilization, and endocrine regulation through growth hormone (GH), insulin-like growth factors (IGF), and IGF-binding proteins (IGFBP). During prolonged thermal exposure, salmon reduced feed intake and growth. Feed utilization was reduced at 19 °C after 45 days compared with fish at lower temperatures, and body lipid storage was depleted with increasing water temperature. Although plasma IGF-1 concentrations did not change, 32-Da and 43-kDa IGFBP increased in fish reared at ≤17 °C, and dropped in fish reared at 19 °C. Muscle igf1 mRNA levels were reduced at 15 and 45 days in fish reared at 15, 17, and 19 °C. Muscle igf2 mRNA levels did not change after 15 days in response to increasing temperature, but were reduced after 45 days. Although liver igf2 mRNA levels were reduced with increasing temperatures after 15 and 45 days, temperature had no effect on igf1 mRNA levels. The liver igfbp2b mRNA level, which corresponds to circulating 43-kDa IGFBP, exhibited similar responses after 45 days. IGFBP of 23 kDa was only detected in plasma in fish reared at 17 °C, and up-regulation of the corresponding igfbp1b gene indicated a time-dependent catabolic response, which was not observed in fish reared at 19 °C. However, higher muscle ghr mRNA levels were detected in fish at 17 and 19 °C than in fish at lower temperatures, indicating lipolytic regulation in muscle. These results show that the reduction of muscle growth in large salmon is mediated by decreased igf1 and igf2 mRNA levels in addition to GH-associated lipolytic action to cope with prolonged thermal exposure. Accordingly, 13 °C appears to be a more optimal temperature for the growth of adult Atlantic salmon at sea.

Concepts: Liver, Insulin-like growth factor 1, Growth hormone, Ocean, Insulin-like growth factor, Atlantic salmon, Anabolism, IGFBP3


The use of “nutritional supplements” containing unapproved substances has become a regular practice in amateur and professional athletes. This represents a dangerous habit for their health once no data about toxicological or pharmacological effects of these supplements are available. Most of them are freely commercialized online and any person can buy them without a medical surveillance. Usually, the steroids intentionally added to the “nutritional supplements” are testosterone analogs with some structural modifications. In this study, the analyzed product was bought online and a new anabolic steroid known as methylstenbolone (2,17α-dimethyl-17β-hydroxy-5α-androst-1-en-3-one) was detected, as described on label. Generally, anabolic steroids are extensively metabolized, thus in-depth knowledge of their metabolism is mandatory for doping control purposes. For this reason, a human excretion study was carried out with four volunteers after a single oral dose to determine the urinary metabolites of the steroid. Urine samples were submitted to enzymatic hydrolysis of glucuconjugated metabolites followed by liquid-liquid extraction and analysis of the trimethylsilyl derivatives by gas chromatography coupled to tandem mass spectrometry. Mass spectrometric data allowed the proposal of two plausible metabolites: 2,17α-dimethyl-16ξ,17β-dihydroxy-5α-androst-1-en-3-one (S1), 2,17α-dimethyl-3α,16ξ,17β-trihydroxy-5α-androst-1-ene (S2). Their electron impact mass spectra are resonable to that of 16-hydroxylated steroids presenting diagnostic ions such as m/z 231 and m/z 218. These metabolites were detectable after one week post administration while unchanged methylstenbolone was only detectable in a brief period of 45 h.

Concepts: Protein, Metabolism, Mass spectrometry, Testosterone, Androgen, Steroid, Anabolic steroid, Anabolism


This study develops the basic idea of Pütter and Bertalanffy addressing the allometric scaling of anabolism and catabolism on somatic growth dynamics. We proposed a standardized form of the Pütter-Bertalanffy equation (PBE), which is given as the extended model of Richards function, and subsequently solved it. The analytical solution of the PBE was defined by an incomplete beta function and can take a wide range of shapes in its growth curve. The mathematical behavior of PBE due to the change in parameter values was briefly discussed. Most forms of solution consistently hold the implicit functional type with respect to the variable of body size.

Concepts: Parameter, Polynomial, Aristotle, Anabolism, Parametric equation, Imperative programming, Gamma function, Beta function


Anabolic agents have been top-ranked for many years among statistics of adverse analytical findings compiled by the World Anti-Doping Agency (WADA). Besides archetypical anabolic-androgenic steroids (AAS), alternative substances with similar effects concerning bone and muscle anabolism have been therapeutically pursued. A prominent emerging class of drugs is the chemically heterogeneous group of selective androgen receptor modulators (SARMs), some of which have been detected in doping control samples between 2009 and 2012 despite missing clinical approval.

Concepts: Metabolism, Testosterone, Androgen, Steroid, Anabolic steroid, Anabolism, Selective androgen receptor modulator, World Anti-Doping Agency