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      Coffee consumption promotes skeletal muscle hypertrophy and myoblast differentiation

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          Abstract

          Coffee increases skeletal muscle function and hypertrophy by regulating the TGF-β/myostatin – Akt – mTORC1.

          Abstract

          Coffee is a widely consumed beverage worldwide and is believed to help prevent the occurrence of various chronic diseases. However, the effect of coffee on skeletal muscle hypertrophy, differentiation and the mechanisms of action responsible have remained unclear. To investigate the effect of coffee on skeletal muscle hypertrophy, mice were fed a normal diet or a normal diet supplemented with 0.3% coffee or 1% coffee. Coffee supplementation was observed to increase skeletal muscle hypertrophy, while simultaneously upregulating protein expression of total MHC, MHC2A, and MHC2B in quadricep muscle. Myostatin expression was also attenuated, and IGF1 was upregulated with subsequent phosphorylation of Akt and mTOR, while AMPK phosphorylation was attenuated. Coffee also increased the grip strength and PGC-1α protein expression, and decreased the expressions of TGF-β and myostatin in tricep muscle. Coffee activated the MKK3/6-p38 pathway and upregulated PGC-1α, which may play a role in promoting myogenic differentiation and myogenin expression in C2C12 cells. These results suggest that coffee increases skeletal muscle function and hypertrophy by regulating the TGF-β/myostatin – Akt – mTORC1.

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          Most cited references48

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          Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size.

          Myostatin is a negative regulator of skeletal muscle size, previously shown to inhibit muscle cell differentiation. Myostatin requires both Smad2 and Smad3 downstream of the activin receptor II (ActRII)/activin receptor-like kinase (ALK) receptor complex. Other transforming growth factor-beta (TGF-beta)-like molecules can also block differentiation, including TGF-beta(1), growth differentiation factor 11 (GDF-11), activins, bone morphogenetic protein 2 (BMP-2) and BMP-7. Myostatin inhibits activation of the Akt/mammalian target of rapamycin (mTOR)/p70S6 protein synthesis pathway, which mediates both differentiation in myoblasts and hypertrophy in myotubes. Blockade of the Akt/mTOR pathway, using small interfering RNA to regulatory-associated protein of mTOR (RAPTOR), a component of TOR signaling complex 1 (TORC1), increases myostatin-induced phosphorylation of Smad2, establishing a myostatin signaling-amplification role for blockade of Akt. Blockade of RAPTOR also facilitates myostatin's inhibition of muscle differentiation. Inhibition of TORC2, via rapamycin-insensitive companion of mTOR (RICTOR), is sufficient to inhibit differentiation on its own. Furthermore, myostatin decreases the diameter of postdifferentiated myotubes. However, rather than causing upregulation of the E3 ubiquitin ligases muscle RING-finger 1 (MuRF1) and muscle atrophy F-box (MAFbx), previously shown to mediate skeletal muscle atrophy, myostatin decreases expression of these atrophy markers in differentiated myotubes, as well as other genes normally upregulated during differentiation. These findings demonstrate that myostatin signaling acts by blocking genes induced during differentiation, even in a myotube, as opposed to activating the distinct "atrophy program." In vivo, inhibition of myostatin increases muscle creatine kinase activity, coincident with an increase in muscle size, demonstrating that this in vitro differentiation measure is also upregulated in vivo.
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            Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle.

            Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.
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              A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease.

              We conducted a systematic review to summarize the epidemiological evidence on the association between cigarette smoking, coffee drinking, and the risk of Parkinson's disease. Case-control and cohort studies that reported the relative risk of physician-confirmed Parkinson's disease by cigarette smoking or coffee drinking status were included. Study-specific log relative risks were weighted by the inverse of their variances to obtain a pooled relative risk and its 95% confidence interval (CI). Results for smoking were based on 44 case-control and 4 cohort studies, and for coffee 8 case-control and 5 cohort studies. Compared with never smokers, the relative risk of Parkinson's disease was 0.59 (95% CI, 0.54-0.63) for ever smokers, 0.80 (95% CI, 0.69-0.93) for past smokers, and 0.39 (95% CI, 0.32-0.47) for current smokers. The relative risk per 10 additional pack-years was 0.84 (95% CI, 0.81-0.88) in case-control studies and 0.78 (95% CI, 0.73-0.84) in cohort studies. Compared with non-coffee drinkers, relative risk of Parkinson's disease was 0.69 (95% CI, 0.59-0.80) for coffee drinkers. The relative risk per three additional cups of coffee per day was 0.75 (95% CI, 0.64-0.86) in case-control studies and 0.68 (95% CI, 0.46-1.00) in cohort studies. This meta-analysis shows that there is strong epidemiological evidence that smokers and coffee drinkers have a lower risk of Parkinson's disease. Further research is required on the biological mechanisms underlying this potentially protective effect.
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                Author and article information

                Journal
                FFOUAI
                Food & Function
                Food Funct.
                Royal Society of Chemistry (RSC)
                2042-6496
                2042-650X
                2018
                2018
                : 9
                : 2
                : 1102-1111
                Affiliations
                [1 ]Division of Nutrition and Metabolism Research
                [2 ]Korea Food Research Institute
                [3 ]Wanjugun
                [4 ]Republic of Korea
                [5 ]Department of Biotechnology
                [6 ]Division of Food Biotechnology
                Article
                10.1039/C7FO01683B
                29359224
                0e7e0c5f-6005-46b5-9042-145a620cd1b5
                © 2018

                http://rsc.li/journals-terms-of-use

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