J Exerc Nutrition Biochem Search

CLOSE


Phys Act Nutr > Volume 21(3); 2017 > Article
Oh, Lee, and Kim: Effects of conjugated linoleic acid/n-3 and resistance training on muscle quality and expression of atrophy-related ubiquitin ligases in middle-aged mice with high-fat diet-induced obesity

Abstract

[Purpose]

To investigate the effects of conjugated linoleic acid (CLA)/n-3 supplements and resistance exercise training (RT) for 20 weeks on muscle quality and genes related to protein synthesis/degradation in middle-aged mice with high-fat diet (HFD)-induced obesity.

[Methods]

Nine-month-old C57BL/6 male mice were randomly assigned to five groups: 1) normal diet (C), 2) high-fat diet (H), 3) H+RT (HRT), 4) H+CLA/n-3 (H-CN), and 5) H+RT+CLA/n-3 (H-RTCN). HFD groups were given a diet containing 60% fat for 20 weeks, and exercised groups underwent progressive RT using weighted ladder climbing. The CLA/n-3 mixed diet contained 1% CLA and 1% n-3. Grip strength was assessed, and triceps were removed. RT-PCR was used to analyze transcript levels.

[Results]

Grip strength of the H group was significantly lower than that of the C group; however, those in the H-CN, H-RT, and H-RTN groups were significantly greater than that in the H group. However, the muscle quality was significantly greater only in the H-RT group compared with the H and H-CN groups. Akt expression decreased in the H-CN, H-RT, and H-RTCN groups compared with those in the C and H groups, whereas mammalian target of rapamycin expression increased in the H, H-CN, H-RT, and H-RTCN groups compared with that in the C group. However, atrogin1 was significantly downregulated in the H-RTCN group compared with that in the H and H-CN groups, and MuRF1 expression was also decreased in the H-RT and H-RTCN groups. Interestingly, atrogin1 and MuRF1 were downregulated in the H-RTCN group compared with that in the H-CN group.

[Conclusion]

HFD-mediated gene expression involved in protein degradation was attenuated following 20-week RT with CLA/n-3. Furthermore, RT with or without CLA/n-3 improved grip strength and muscle quality in middle-aged mice during HFD. Therefore, RT with CLA/n-3 during HFD may improve muscle strength and quality by suppressing protein degradation.

INTRODUCTION

Obesity is a serious health problem that can be regulated through various approaches, such as scientific, pharmacological, and nutritional/exercise interventions, as well as improvement of lifestyle. Obesity induces negative regulation of genes related to protein synthesis/degradation in skeletal muscle tissue, consistent with the observation of decreased lean body mass and increased fat mass in the aged population. Sarcopenic obesity refers to a new trend in aged individuals who simultaneously demonstrate reductions and increases in lean mass and fat mass, respectively, leading to poor quality of life. High density energy intake (i.e., a high-fat diet) with limited physical activity (i.e., a sedentary life style) induces negative alterations in body composition, possibly leading to early onset of the sarcopenic process.
Maintaining muscle mass is a balance between protein synthesis and protein degradation systems, involving molecular mechanisms that regulate muscle growth and atrophy1. There are several signaling pathways that regulate muscle protein synthesis/degradation. Insulin-like growth factor 1 (IGF1), a major activator of muscle hypertrophy, induces an increase in muscle mass by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, resulting in the activation of downstream effector proteins2, 3. When IGF1 binds to its receptor, insulin receptor substrate-1 (IRS-1) is activated, followed by PI3K activation through conversion of intramembranous phosphoinositide-(4,5)-biphosphate to phosphoinositide-(3,4,5)-triphosphate (PIP3)4. Subsequently, Akt binds PIP3 and is activated by phosphoinositide-dependent kinase-1 (PDK1). Akt is then released into the cytosol to activate mTOR through PDK1. Akt plays an important role in skeletal muscle hypertrophy via activation of mTOR and glycogen synthase kinase 3β5. In contrast, muscle atrophy is associated with an increase in several proteins that promote proteolysis, such as atrogin-1 and Murf-1, while increasing the degradation of myofibrillar protein6. Additionally, inhibition of the PI3K/Akt/mTOR signaling pathway is involved in the synthesis of related proteins and accompanied by suppression of muscle protein synthesis7, 8.
In many studies, long-term regular exercise interventions are considered an important tool for the prevention and treatment of obesity. In particular, resistance exercise training (RT) is an effective intervention to combat sarcopenia by enhancing myofiber hypertrophy and improving muscle strength, power, and mobility9. Muscle quality, referred to as specific tension, is a measure of the strength per unit of muscle mass10 and may be a better indicator of muscle function than strength alone11.
Conjugated linoleic acid (CLA) and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have received much attention for their anti-obesity effects12-15. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in long-chain omega-3 fatty acids are major factors affecting metabolism and inflammation. In particular, EPA has been shown to reduce triglycerides and improve blood lipid profiles17, and DHA has been reported to enhance lipid oxidation and insulin sensitivity through activation of AMP-activated protein kinase signaling in skeletal muscle15. In addition, many studies have reported that CLA increases appetite suppression and fatty acid oxidation16, 18-20. Specifically, in animal models of obesity induced by a high-fat diet (HFD), CLA treatment not only compensates for body weight gain, but also increases fatty acid oxidation with a decrease in blood insulin concentrations19. Similarly, many studies have reported that CLA treatment induces changes in body composition, decreasing body weight and body fat and increasing lean body mass20-25. However, the trans-10 and cis-12 isomers of CLA induce liver hypertrophy and steatosis, and studies have shown that insulin sensitivity is reduced26-29. In contrast, n-3 has been reported to prevent obesity and improve insulin sensitivity30. In fact, studies have shown that n-3 intake counteracts the side effects of CLA treatment31. Intake of CLA and n-3 also enhances the benefits induced by RT, including increased skeletal muscle mass32 and muscle strength33, 34. However, Lee and colleagues35 reported that CLA plus n-3 intake did not prevent the reduction in muscle strength and mass due to long-term HFD.
Although CLA and n-3 have attracted interest because of their health-enhancing benefits, few studies have examined muscle quality and gene expression related to protein synthesis and degradation in skeletal muscle with RT in middle-aged mice with HFD-induced obesity. Additionally, their efficacy in attenuating HFD-induced impairments in skeletal muscle remains poorly understood. Therefore, the purpose of this study was to investigate the effects of CLA/n-3 supplements and RT for 20 weeks on muscle quality and genes related to protein synthesis/degradation in middle-aged mice with HFD-induced obesity.

METHODS

Animals and experimental design

Nine-month-old C57BL/6 male mice were randomly assigned to one of five groups: 1) normal diet control (C, n = 7), 2) HFD control (H, n = 5), 3) HFD with CLA/n-3 (H-CN, n = 9), 4) HFD with RT (H-RT, n = 9), and 5) HFD with RT and CLA/n-3 (H-RTCN, n = 8). All groups except the C group were fed an HFD for 20 weeks. Each group received an HFD alone (H), HFD with CLA/n-3 (H-CN), HFD with RT (H-RT), or HFD with RT and CLA/n-3 combined treatment (H-RTCN) for 20 weeks (Fig. 1). The animals were housed individually in stainless steel cages maintained at 22-24°C with a 12:12 h light:dark cycle. After consumption of the specific diet for 5 months, animals were sacrificed, and muscles were harvested. All procedures were approved by the institutional Animal Care and Use Committee of Florida State University.
Table 1.

The results of body weight, triceps weight, grip strength, and muscle quality.

C (n=7) H (n=5) H-CN (n=9) H-RT (n=9) H-RTCN (n=8) F
Pre BW, g 32.23±0.75 30.00±1.06 30.98±0.72 31.23±0.73 31.51±0.87 0.794
Post BW, g 29.84±0.77 46.94±1.01### 33.19±2.16††† 42.27±1.42###‡‡‡ 38.00±1.77##†† 14.500***
Pre Fat mass, g 14.14±0.86 12.00±1.52 14.00±0.67 13.56±1.00 14.00±1.35 0.509
Post Fat mass, g 15.86±1.26 30.40±1.63### 17.44±1.14††† 32.22±1.80###‡‡‡ 19.63±1.13†††¥¥¥ 28.002***
Triceps/BW, mg/g 35.73±1.59 24.51±2.58### 31.25±1.34#††¥¥ 25.28±1.05###‡‡ 33.66±1.56††¥¥¥ 9.906***
Grip Strength/ BW, g/g 48.34±1.13 27.49±1.10### 39.24±2.87#†† 39.64±2.14#†† 47.26±3.64†††¥ 21.075***
Muscle quality, g/mg 136.52±5.23 119.38±17.25 125.44±6.45 158.99±11.10 140.98±9.69 2.439

Values are mean ± standard errors. C, normal diet control; H, high fat diet; H-CN, high fat diet with CLA/n-3; H-RT, high fat diet with resistance training; H-RTCN, high fat diet with CLA/n-3 supplement and resistance training.

*p<.05, significant differences among groups

#p<.05, significantly different from C;

†p<.05, significantly different from H

‡p<.05, significantly different from H-CN

¥p<.05, significantly different from H-RT

Figure 1.

Overall Research Design.

JENB_2017_v21n3_11_f001.jpg
Figure 2.

Relative RT-PCR results for genes expression related to protein synthesis/degradation using 18S ribosomal RNA as an internal standard.

JENB_2017_v21n3_11_f002.jpg

RT

The mice in the exercise groups (H-RT and H-RTCN) were trained to climb a 1-m vertical ladder with an 85° incline three times per week for 20 weeks. During the first week, they were familiarized with climbing up to the top of the ladder with and without weight on their tails. Training sessions were commenced with intensity at 50% body weight (about 15 g) and increased by 1% body weight on a biweekly basis. They performed four sets of three reps (about 38 contractions) with 1-min rest intervals between repetitions and 2-min intervals between sets, 3 days per week for 20 weeks, as described in our previous studies35-37.

CLA/n-3 mix intake

The C group was fed a normal diet (10% fat by energy, 3.8 kcal/g), whereas the HFD groups were given 60% fat (5.2 kcal/g) for 20 weeks, as previously described35-37. The CLA/n-3 mixed diet contained 1% CLA (50:50 mix of cis-9, trans-11:trans-10, cis-12) and 1% PUFAs enriched in n-3 fatty acids. Fresh diet was prepared weekly, stored in sealed plastic bags at -20°C to minimize oxidation, and provided daily ad libitum.

Muscle strength and quality

Muscle strength was measured using a grip strength meter for animals (DFS-101; AMETEK, CA, USA) as previously described35-37. All mice adapted with dual grip bars connected to separate strain gauges to allow separate measurements of force with the forelimbs. For each trial, the mice were placed on the dual grip bar and then pulled gently by the scruff of the neck and base of the tail, in a rearward direction, away from the bar. The applied force at the point at which the mouse released its grip for each paw was recorded by two separate strain gauges connected to a digital readout. Grip strength was tested in three trials, and the greatest force was used for analysis; the values were represented as the ratio of strength in grams to body weight in grams. There are several ways to assess muscle quality, and we used the ratio of strength to muscle mass10, 38. We defined muscle quality as the ratio of grip strength in grams to triceps wet weight in milligrams.

Tissue collection

All animals were deeply anesthetized using a 4.0-4.5% isoflurane gas with breathing medical air, maintained with 2.0% isoflurane during muscle collection, and then sacrificed at least 3 days after training sessions to exclude any short-term effects of exercise. The tissues were collected from triceps. The samples were quickly weighed, snap frozen with liquid nitrogen, and then stored at -80°C for mRNA analysis.

RNA isolation and reverse transcription polymerase chain reaction (RT-PCR)

Transcript levels of target factors was assessed using RT-PCR as previously developed39. First, total RNA was extracted from triceps using a commercial TRI reagent, and 1 μg RNA was reverse transcribed into cDNA. The primer sequences for PCR were as follows: IGF1 (fwd) 5′-TCCTTATGAATTGGCTTATC-3′, (rev) 5′-GTTTGTCATCTTCCATTCTGTT-3′; AKT (fwd) 5′-CGGCCACGCTACTTCCTCCTC-3′, (rev) 5′-GCCCATTCTTCCCGCTCCTCAG- 3′; mTOR (fwd) 5′-GCCCACGCCTGCCATACTTG- 3′, (rev) 5′-TCAGCTCCTCAGCTCC G G G T C T T C C T T G T T- 3 ′ ; atrogin -1 ( fwd) 5′-CGTGCACGGCCAACAACC-3′, (rev) 5′-CCCGCCAACGTCTCCTCAAT- 3′; MuRF1 (fwd) 5′-GGCTGCGAATCCCTACTGG- 3′, (rev) 5′-TGATCTTCTCGTCTTCGTGTTCCT- 3′. For each PCR assay, 18S was amplified with each target mRNA, yielding a target mRNA/18S ratio. The PCR products were separated by electrophoresis on 2% agarose gels and visualized by ethidium bromide for band sizes and product purity.

Statistical analysis

All data are presented as means ± standard errors, with significance set at p < 0.05. The differences between groups were analyzed using one-way analysis of variance and post-hoc least significant difference comparisons. Statistical analysis was performed using Origin 8.0 and SPSS version 18.0 software.

RESULTS

There were significant differences in changes in body weight and fat mass after 20 weeks of treatment among the groups (p < 0.001). After 20 weeks, body weight was significantly increased in the H (+57.31%, p < 0.001), H-RT (+41.66%, p < 0.001), and H-RTCN groups (+27.35%, p = 0.002) compared with that in the C group. However, there were no significant differences in body weight at 20 weeks between the C and H-CN groups. In addition, body weights after 20 weeks were significantly lower in the H-CN (-29%, p < 0.001) and H-RTCN groups (-19%, p = 0.002) compared with that in the H group. Fat mass at 20 weeks was also higher in the H (+91.68%, p < 0.001), H-RT (+103.15%, p < 0.001), and H-RTCN groups (+23.77%, p = 0.076) than in the C group. However, fat mass was significantly reduced in the H-CN (-42.63%, p < 0.001) and H-RTCN groups (-35.43%, p < 0.001) compared with that in the H group.
The weights of triceps did not significantly differ among groups (C: 106.34 ± 4.51 mg, H: 115.79 ± 14.07 mg, H-CN: 101.95 ± 4.77 mg, H-RT: 106.84 ± 5.61 mg, H-RTCN: 127.13 ± 6.53 mg; p = 0.069); however, normalizing the triceps weight to body weight yielded significant differences among groups (p < 0.001). Significantly decreased relative triceps weights were observed in the H (-31%, p < 0.001), H-CN (-13%, p = 0.042), and H-RT groups (-29%, p < 0.001) compared with that in the C group. Additionally, relative triceps weight was significantly higher in the H-CN (+27%, p = 0.007) and H-RTCN groups (+37%, p = 0.001) than in the H group.
Grip strength in the H group was significantly lower than in the C group (+76%, p < 0.001); in contrast, grip strength in the H-CN (+43%, p = 0.007), H-RT (+44%, p = 0.005), and H-RTCN groups (+73%, p < 0.001) was significantly greater than that in the H group. In particular, grip strength in the H-RTCN group was significantly greater than those in the H-CN (+20%, p = 0.03) and H-RT groups (+19%, p = 0.038). Muscle quality was significantly greater in the H-RT group than in the H (+33%, p = 0.013) and H-CN groups (+27%, p = 0.013), although there were no significant differences among groups (p = 0.066).
Although there were no significant differences in IGF1 mRNA expression among groups, Akt mRNA expression decreased in the H-CN (versus C: -22%, p = 0.022), H-RT (versus C: -34%, p = 0.001; versus H: -32%, p = 0.004), and H-RTCN groups (versus C: -31%, p = 0.003; versus H: -29%, p = 0.011). Additionally, mTOR mRNA expression increased in the H (+97%, p = 0.012), H-CN (+117%, p = 0.001), H-RT (+94%, p = 0.006), and H-RTCN groups (+104%, p = 0.005) compared with that in the C group, and atrogin1 expression was significantly decreased in the H-RTCN group compared with that in the H group (p = 0.006) and H-CN groups (p = 0.004) by 37% and 34%, respectively. MuRF1 expression was decreased in the H-RT (versus C: -34%, p = 0.011; versus H: 37%, p = 0.01) and H-RTCN groups (versus C: -66%, p < 0.001; versus H: -67%, p < 0.001; versus H-CN: -57%, p = 0.001; versus H-RT: -48%, p = 0.019). Interestingly, significant decreases in atrogin1 (-34%, p = 0.004) and MuRF1 expression (-57%, p = 0.001) were observed in the H-RTCN group compared with that in the H-CN group.

DISCUSSION

HFD reduces muscle function and induces muscle atrophy and obesity35-37, 40. Regular CLA or n-3 treatment has been reported to reduce body fat mass in healthy adults, normal-weight healthy exercising adults, and overweight and obese adults21-25, 29, 41-44. However, many other studies have also reported that CLA or n-3 intake did not significantly affect body fat or lean body mass in lean or nonobese subjects and older adults28, 45. These different results indicate that the effects of CLA and n-3 supplements may vary with age, sex, obesity, physical activity level, and consumption duration. In the present study, we found that HFD for 20 weeks induced obesity (57.31% weight gain and 91.68% fat gain) and decreased skeletal muscle mass relative to body weight, whereas CLA plus n-3 supplementation with or without RT attenuated weight gain and skeletal muscle wasting. Furthermore, the 20-week HFD induced a reduction in muscle strength relative to body weight, whereas RT, CLA/n-3, and combined RT with CLA/n-3 prevented the decrease in muscle strength induced by HFD in middle-aged mice.
Muscle atrophy induced by an HFD is explained through various mechanisms, including an imbalance between protein synthesis and degradation. The ubiquitin proteasome system catalyzes the degradation of most cellular proteins46 and is one of the major pathways regulating muscle protein degradation; this system plays a central role in controlling muscle size1. Atrogin1 and MuRF1 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle. Although we did not find a significant increase in the expression of atrogin1 or MuRF1 after 20 weeks of HFD, these targets tended to show increased expression after consumption of the HFD. In fact, we found that RT with or without CLA/n-3 intake decreased atrogin1 and MuRF1 mRNA expression in skeletal muscle induced by the HFD in middle-aged mice. Moreover, the expression of atrophy-related genes was not significantly increased after long-term HFD. Interestingly, Sandri et al.47 reported that the isometric force of the gastrocnemius muscle and force per muscle weight was lower in atrogin1- and MuRF1-knockout mice at 15 and 26 months of age, respectively. These results indicated that the absence of the atrophy-related ubiquitin ligases atrogin1 and MuRF1 decreased force generation during isometric contraction. However, our results showed that RT with or without CLA/n-3 intake reduced muscle strength and quality, and these effects were exacerbated by consumption of the HFD, accompanied by decreases in atrogin1 and MuRF1 expression. The lack of atrogin1 and MuRF1 expression has been reported to prevent muscle atrophy in denervation mice3. In addition, atrogin1-knockdown mice48 and MuRF1-knockout mice49, which show increased muscle loss following fasting and dexamethasone administration, respectively, showed resistance to muscle atrophy. Taken together, these findings suggested that specific atrophy-related ubiquitin ligases may be expressed differently depending on the stage of the atrophy process and the model of muscle atrophy, e.g., immobilization, denervation, fasting, HFD, dexamethasone, or catabolic conditions. These genes may also be expressed differently depending on age, sex, and muscle type because these factors are known to affect muscle mass and strength. Various transcription factors, such as Smad3, p38 mitogen-activated protein kinase, and FoxO signaling, regulate the expression of atrogin1 and MuRF1 genes. In order to clarify differences in the expression of atrophy-related ubiquitin ligases, it will be necessary to analyze the various transcription factors together.
In our study, the expression of mTOR mRNA was significantly increased in the experimental groups compared with that in the control group consuming a normal diet; in contrast, differences in the expression of IGF1 and Akt mRNA were not observed in HFD-induced obesity. Long-term CLA-n3 intake with or without RT was shown to decrease Akt expression and increase mTOR expression in mice fed an HFD. To date, the results of studies on the Akt/mTOR signaling pathway targeting animal models have been controversial. Despite the decrease in skeletal muscle mass due to aging50-52, Akt activation has been reported to be decreased50, 53, unchanged51, 54, or increased52. Skeletal muscle proteins consistently undergo metabolic turnover, muscle protein synthesis, and protein degradation, and the amount of protein is determined by the relative rate of protein synthesis and proteolysis. Changes in body composition due to metabolic conditions such as aging and obesity induce negative regulation of genes related to various signaling pathways and leading to an imbalance in protein synthesis/degradation in skeletal muscle. In order to clarify differences in expression of hypertrophy-related genes, it will be necessary to analyze the regenerative capacity of satellite cells, turnover of damaged mitochondria, and nuclear apoptosis simultaneously. Finally, this study had some limitations, making it difficult to compare directly with the results of previous studies, because we induced changes in body composition by long-term HFD, exercise intervention, and nutritional treatment together at the same time.

CONCLUSION

HFD-mediated expression of genes involved in protein degradation was attenuated following 20-week RT with CLA/n-3 supplementation. Furthermore, CLA/n-3 with or without RT prevented weight gain, and RT with or without CLA/n-3 improved grip strength and muscle quality in middle-aged mice during HFD, albeit to a lesser degree for the latter. Therefore, RT with CLA/n-3 supplementation during HFD may improve muscle strength and quality by suppressing protein degradation. Future research is needed to verify these findings in middle-aged obese men and women.

Acknowledgments

This work was supported by a grant from the National Research Foundation of Korea funded by the Korean Government (NRF- 2014S1A5B5A07042751).

References

1.
Gumucio JP and Mendias CL. Atrogin-1, MuRF-1, and sarcopenia. Endocrine. 2013;43:12-21.
crossref pdf
Gumucio JP, et al, Mendias CL. Atrogin-1, MuRF-1, and sarcopenia. Endocrine 2013;43:12-21. PMID: 10.1007/s12020-012-9751-7. PMID: 22815045.
2.
Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell B. 37:1974-84, 2005.
crossref
Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell B 37;1974-84:2005.
3.
Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001; 294:1704-8.
crossref
Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001;294:1704-8. PMID: 10.1126/science.1065874. PMID: 11679633.
4.
Schiaffino S and Mammucari C. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle. 2011;1: 4.
crossref
Schiaffino S, et al, Mammucari C. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle 2011;1:4PMID: 10.1186/2044-5040-1-4. PMID: 21798082.
5.
Fernandes, T, Úrsula PR Soci, Stéphano FS Melo, Cléber RA, Edilamaar OM. Signaling pathways that mediate skeletal muscle hypertrophy: Effects of exercise training. INTECH Open Access Publ. 2012.
crossref
Fernandes T, Úrsula PR Soci, Stéphano FS Melo, Cléber RA, Edilamaar OM. Signaling pathways that mediate skeletal muscle hypertrophy: Effects of exercise training. INTECH Open Access Publ 2012.
6.
Jackman RW and Karndarian SC. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol.2004;287:C834-C43.
crossref
Jackman RW, et al, Karndarian SC. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 2004;287:C834-C43. PMID: 10.1152/ajpcell.00579.2003. PMID: 15355854.
7.
Gomes MD , Lecker SH , Jagoe RT , Navon A , Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA. 2001;98:14440-5.
crossref
Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 2001;98:14440-5. PMID: 10.1073/pnas.251541198. PMID: 11717410.
8.
Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, Lin HC, Yancopoulos GD, Glass DJ. Insulin-like growth factor-1 (IGF-1): inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem, 2005;280:2737-44.
crossref
Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, Lin HC, Yancopoulos GD, Glass DJ. Insulin-like growth factor-1 (IGF-1): inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem 2005;280:2737-44. PMID: 10.1074/jbc.m407517200. PMID: 15550386.
9.
Kim JS, Kosek DJ, Petrella JK, Cross JM, Bamman MM. Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women. J Appl Physiol. 2005;99:2149-58.
crossref
Kim JS, Kosek DJ, Petrella JK, Cross JM, Bamman MM. Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women. J Appl Physiol 2005;99:2149-58. PMID: 10.1152/japplphysiol.00513.2005. PMID: 16051712.
10.
Lynch NA, Metter EJ, Lindle RS, Fozard JL, Tobin JD, Roy TA, Fleg JL, Hurley BF. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol. 1999;86:188-94.
crossref
Lynch NA, Metter EJ, Lindle RS, Fozard JL, Tobin JD, Roy TA, Fleg JL, Hurley BF. Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol 1999;86:188-94. PMID: 9887130.
11.
Dutta C, Hadley EC, Lexell J. Sarcopenia and physical performance in old age: overview. Muscle Nerve Suppl. 1997;5:S5-9.
crossref
Dutta C, Hadley EC, Lexell J. Sarcopenia and physical performance in old age: overview. Muscle Nerve Suppl 1997;5:S5-9. PMID: 9331374.
12.
Arai T, Kim HJ, Chiba H, Matsumoto A. Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice. J Atheroscler Thromb. 2009;16:674-83.
crossref
Arai T, Kim HJ, Chiba H, Matsumoto A. Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice. J Atheroscler Thromb 2009;16:674-83. PMID: 10.5551/jat.1313. PMID: 19907107.
13.
Calder PC. Fatty acids and inflammation: The cutting edge between food and pharma. Eur J Pharmacol. 2011;668:S50-8.
crossref
Calder PC. Fatty acids and inflammation: The cutting edge between food and pharma. Eur J Pharmacol 2011;668:S50-8. PMID: 10.1016/j.ejphar.2011.05.085. PMID: 21816146.
14.
Fedor D, Kelley DS. Prevention off insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 2009;12:138-46.
crossref
Fedor D, Kelley DS. Prevention off insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 2009;12:138-46. PMID: 10.1097/mco.0b013e3283218299. PMID: 19202385.
15.
Lam YY, Hatzinikolas G, Weir JM, Janovská A, McAinch AJ, Game P, Meikle PJ, Wittert GA. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: The effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids. Biochim Biophys Acta. 2011;1811:468-75.
crossref
Lam YY, Hatzinikolas G, Weir JM, Janovská A, McAinch AJ, Game P, Meikle PJ, Wittert GA. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: The effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids. Biochim Biophys Acta 2011;1811:468-75. PMID: 10.1016/j.bbalip.2011.04.011. PMID: 21570480.
16.
Vemuri M, Kelley DS, Mackey BE, Rasooly R, Bartolini G. Docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) prevents trans-10, cis-12 conjugated linoleic acid (CLA) - Induced insulin resistance in mice. Metab Syndr Relat Disord. 2007;5:315-22.
crossref
Vemuri M, Kelley DS, Mackey BE, Rasooly R, Bartolini G. Docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) prevents trans-10, cis-12 conjugated linoleic acid (CLA) - Induced insulin resistance in mice. Metab Syndr Relat Disord 2007;5:315-22. PMID: 18370801.
17.
Zaima N, Sugawara T, Goto D, Hirata T. Trans geometric isomers of EPA decrease LXR alpha-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1 beta. J Lipid Res. 2006;47:2712-7.
crossref
Zaima N, Sugawara T, Goto D, Hirata T. Trans geometric isomers of EPA decrease LXR alpha-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1 beta. J Lipid Res 2006;47:2712-7. PMID: 17005995.
18.
Chung S, Brown JM, Sandberg MB, McIntosh M. Trans-10, cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling. J Lipid Res. 2005;46:885-95.
crossref
Chung S, Brown JM, Sandberg MB, McIntosh M. Trans-10, cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling. J Lipid Res 2005;46:885-95. PMID: 10.1194/jlr.m400476-jlr200. PMID: 15716587.
19.
Larsen TM, Toubro S, Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res. 2003;44:2234-41.
crossref
Larsen TM, Toubro S, Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res 2003;44:2234-41. PMID: 12923219.
20.
Li JJ, Huang CJ, Xie D. Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Mol Nutr Food Res. 2008;52:631-45.
crossref
Li JJ, Huang CJ, Xie D. Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Mol Nutr Food Res 2008;52:631-45. PMID: 10.1002/mnfr.200700399. PMID: 18306430.
21.
West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol. 1998;275:R667-72.
crossref
West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol 1998;275::R667-72. PMID: 9728060.
22.
Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes. 2001;50:1149-57.
crossref
Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 2001;50:1149-57. PMID: 10.2337/diabetes.50.5.1149. PMID: 11334420.
23.
Blankson H, Stakkestad JA, Fagertun H et al. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr. 130:2943-8, 2000.
crossref pdf
Blankson H, Stakkestad JA, Fagertun H, et al. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 130;2943-8:2000.
24.
Risérus U,Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes. 2001;25:1129-35.
crossref pdf
Risérus U, Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes 2001;25:1129-35. PMID: 10.1038/sj.ijo.0801659.
25.
Thom E, Wadstein J, Gudmundsen O. Conjugated Linoleic Acid Reduces Body Fat in Healthy Exercising Humans. J Int Med Res. 2001;29:392-6.
crossref
Thom E, Wadstein J, Gudmundsen O. Conjugated Linoleic Acid Reduces Body Fat in Healthy Exercising Humans. J Int Med Res 2001;29:392-6. PMID: 10.1177/147323000102900503. PMID: 11725826.
26.
DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol. 1999;276:R1172-9.
crossref
DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol 1999;276:R1172-9. PMID: 10198400.
27.
Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004;80:887-95.
crossref pdf
Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr 2004;80:887-95. PMID: 15447895.
28.
Risérus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care. 2002;25:1516-21.
crossref
Risérus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 2002;25:1516-21. PMID: 12196420.
29.
Risérus U, Vessby B, Arner P, Zethelius B. Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia. 2004;47:1016-9.

Risérus U, Vessby B, Arner P, Zethelius B. Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia 2004;47:1016-9. PMID: 15168020.
30.
Ikemoto S, Takahashi M, Tsunoda N, Maruyama K, Itakura H, Ezaki O. High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils. Metabolism. 1996;45:1539-46.
crossref
Ikemoto S, Takahashi M, Tsunoda N, Maruyama K, Itakura H, Ezaki O. High-fat diet-induced hyperglycemia and obesity in mice: differential effects of dietary oils. Metabolism 1996;45:1539-46. PMID: 10.1016/s0026-0495(96)90185-7. PMID: 8969289.
31.
Ide T. Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Diabetes. 2005;54:412-23.
crossref
Ide T. Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Diabetes 2005;54::412-23. PMID: 10.2337/diabetes.54.2.412. PMID: 15677499.
32.
Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello GA. The effects of conjugated linoleic acid supplementation during resistance training. Med Sci Sports Exerc. 2006;38:339-48.
crossref
Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB, Facci M, Farthing JP, Zello GA. The effects of conjugated linoleic acid supplementation during resistance training. Med Sci Sports Exerc 2006;38:339-48. PMID: 10.1249/01.mss.0000183860.42853.15. PMID: 16531905.
33.
Da Boit M, Sibson R, Sivasubramaniam S, Meakin JR, Greig CA, Aspden RM, Thies F, Jeromson S, Hamilton DL, Speakman JR, Hambly C, Mangoni AA, Preston T, Gray SR. Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial. Am J Clin Nutr. 2017;105:151-8.
crossref
Da Boit M, Sibson R, Sivasubramaniam S, Meakin JR, Greig CA, Aspden RM, Thies F, Jeromson S, Hamilton DL, Speakman JR, Hambly C, Mangoni AA, Preston T, Gray SR. Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial. Am J Clin Nutr 2017;105:151-8. PMID: 10.3945/ajcn.116.140780. PMID: 27852617.
34.
Rodacki CL, Rodacki AL, Pereira G, Naliwaiko K, Coelho I, Pequito D, Fernandes LC. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr. 2012;95:428-36.
crossref pdf
Rodacki CL, Rodacki AL, Pereira G, Naliwaiko K, Coelho I, Pequito D, Fernandes LC. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr 2012;95:428-36. PMID: 10.3945/ajcn.111.021915. PMID: 22218156.
35.
Lee SR, Khamoui AV, Jo E, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Effect of onjugated linoleic acids and omega-3 fatty acids with or without resistance training on muscle mass in high fat diet-fed middle-aged mice. Exp Physiol. 2017 Aug 10.
crossref
Lee SR, Khamoui AV, Jo E, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Effect of conjugated linoleic acids and omega-3 fatty acids with or without resistance training on muscle mass in high fat diet-fed middle-aged mice. Exp Physiol 2017;8 10.
36.
Lee SR, Jo E, Khamoui AV, Park BS, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Resistance Training and CLA/n-3 Administration Improve Myofiber Size and Myogenic Capacity in High Fat Diet-Fed Mice. FASEB J. 2013;27:1152.26.
crossref
Lee SR, Jo E, Khamoui AV, Park BS, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Resistance Training and CLA/n-3 Administration Improve Myofiber Size and Myogenic Capacity in High Fat Diet-Fed Mice. FASEB J 2013;27:1152.26.
37.
Lee SR, Khamoui AV, Jo E, Park BS, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Effects of chronic high-fat feeding on skeletal muscle mass and function in middle-aged mice. Aging Clin Exp Res. 2015;27:403-11.
crossref pdf
Lee SR, Khamoui AV, Jo E, Park BS, Zourdos MC, Panton LB, Ormsbee MJ, Kim JS. Effects of chronic high-fat feeding on skeletal muscle mass and function in middle-aged mice. Aging Clin Exp Res 2015;27:403-11. PMID: 10.1007/s40520-015-0316-5. PMID: 25647784.
38.
Brooks N, Layne JE, Gordon PL, Roubenoff R, Nelson ME, Castaneda-Sceppa C. Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes. Int J Med Sci. 2007;4:19-27.
crossref
Brooks N, Layne JE, Gordon PL, Roubenoff R, Nelson ME, Castaneda-Sceppa C. Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes. Int J Med Sci 2007;4:19-27.
39.
Adams GR, Haddad F, Baldwin KM, Time course of changes in markers of myogenesis in overloaded rat skeletal muscles. J Appl Physiol. 1999;87:1705-12.
crossref
Adams GR, Haddad F, Baldwin KM. Time course of changes in markers of myogenesis in overloaded rat skeletal muscles. J Appl Physiol 1999;87:1705-12. PMID: 10562612.
40.
Shpilberg Y, Beaudry JL, D’Souza A, Campbell JE, Peckett A, Riddell MC. A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding. Dis Model Mech. 2012;5:671-80.
crossref
Shpilberg Y, Beaudry JL, D’Souza A, Campbell JE, Peckett A, Riddell MC. A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding. Dis Model Mech 2012;5:671-80. PMID: 10.1242/dmm.008912. PMID: 22184636.
41.
Smedman A, Vessby B. Conjugated linoleic acid supplementation in humans-metabolic effects. Lipids. 2001;36: 773-81.
crossref
Smedman A, Vessby B. Conjugated linoleic acid supplementation in humans-metabolic effects. Lipids 2001;36::773-81. PMID: 10.1007/s11745-001-0784-7. PMID: 11592727.
42.
Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord. 1997;21:37-43.
crossref pdf
Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord 1997;21::37-43. PMID: 10.1038/sj.ijo.0800451. PMID: 9023599.
43.
Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, Berra B. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids. Eur J Clin Invest. 2005;35:499-507.
crossref
Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, Berra B. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids. Eur J Clin Invest 2005;35:499-507. PMID: 10.1111/j.1365-2362.2005.01540.x. PMID: 16101670.
44.
Hill AM, Buckley JD, Murphy KJ, Howe PR. Combining fishoil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am J Clin Nutr. 2007;85:1267-74.
crossref pdf
Hill AM, Buckley JD, Murphy KJ, Howe PR. Combining fishoil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am J Clin Nutr 2007;85:1267-74. PMID: 17490962.
45.
Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids. 2000;35:777-82.
crossref
Zambell KL, Keim NL, Van Loan MD, Gale B, Benito P, Kelley DS, Nelson GJ. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 2000;35:777-82. PMID: 10.1007/s11745-000-0585-z. PMID: 10941879.
46.
Kirk-Ballard H, Kilroy G, Day BC, Wang ZQ, Ribnicky DM, Cefalu WT, Floyd ZE. An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: Potential role in the treatment of sarcopenic obesity. Nutrition. 2014;30:S21-5.
crossref
Kirk-Ballard H, Kilroy G, Day BC, Wang ZQ, Ribnicky DM, Cefalu WT, Floyd ZE. An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: Potential role in the treatment of sarcopenic obesity. Nutrition 2014;30:S21-5. PMID: 10.1016/j.nut.2014.02.027. PMID: 24985101.
47.
Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, Pion D, Roceri M, Romanello V, Serrano AL, Toniolo L, Larsson L, Maier AB, Muñoz-Cánoves P, Musarò A, Pende M, Reggiani C, Rizzuto R, Schiaffino S. Signalling pathways regulating muscle mass in ageing skeletal muscle: The role of the IFG1-AktmTOR-FoxO pathway. Biogerontology. 2013;14:303-23.
crossref pdf
Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, Pion D, Roceri M, Romanello V, Serrano AL, Toniolo L, Larsson L, Maier AB, Muñoz-Cánoves P, Musarò A, Pende M, Reggiani C, Rizzuto R, Schiaffino S. Signalling pathways regulating muscle mass in ageing skeletal muscle: The role of the IFG1-AktmTOR-FoxO pathway. Biogerontology 2013;14:303-23. PMID: 23686362.
48.
Cong H, Sun L, Liu C, Tien P. Inhibition of atrogin-1/MAFbx expression by adenovirus-delivered small hairpin RNAs attenuates muscle atrophy in fasting mice. Hum Gene Ther. 2011;22:313-24.
crossref
Cong H, Sun L, Liu C, Tien P. Inhibition of atrogin-1/MAFbx expression by adenovirus-delivered small hairpin RNAs attenuates muscle atrophy in fasting mice. Hum Gene Ther 2011;22:313-24. PMID: 10.1089/hum.2010.057. PMID: 21126200.
49.
Baehr LM, Furlow JD, Bodine SC Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids. J Physiol. 2011;589:4759-76.
crossref
Baehr LM, Furlow JD, Bodine SC. Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids. J Physiol 2011;589:4759-76. PMID: 10.1113/jphysiol.2011.212845. PMID: 21807613.
50.
Haddad F, Adams GR. Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J Appl Physiol. 2006;100:1188-203.
crossref
Haddad F, Adams GR. Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J Appl Physiol 2006;100:1188-203. PMID: 16373446.
51.
Edstrom E, Altun M, Hagglund M, Ulfhake B. Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle. J Gerontol Ser A Biol Sci Med Sci. 2006;61:663-74.
crossref pdf
Edstrom E, Altun M, Hagglund M, Ulfhake B. Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle. J Gerontol Ser A Biol Sci Med Sci 2006;61:663-74. PMID: 10.1093/gerona/61.7.663. PMID: 16870627.
52.
Gaugler M, Brown A, Merrell E, DiSanto-Rose M, Rathmacher JA, Reynolds TH 4th. PKB signaling and atrogene expression in skeletal muscle of aged mice. J Appl Physiol. 2011;111:192-9.
crossref
Gaugler M, Brown A, Merrell E, DiSanto-Rose M, Rathmacher JA. Reynolds TH 4th. PKB signaling and atrogene expression in skeletal muscle of aged mice. J Appl Physiol 2011;111:192-9. PMID: 21551011.
53.
Clavel S, Coldefy AS, Kurkdjian E, Salles J, Margaritis I, Derijard B. Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle. Mech Ageing Dev. 2006;127:794-801.
crossref
Clavel S, Coldefy AS, Kurkdjian E, Salles J, Margaritis I, Derijard B. Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle. Mech Ageing Dev 2006;127:794-801. PMID: 10.1016/j.mad.2006.07.005. PMID: 16949134.
54.
Rahnert JA, Luo Q, Balog EM, Sokoloff AJ, Burkholder TJ. Changes in growth-related kinases in head, neck and limb muscles with age. Exp Gerontol. 2011;46:282-91.
crossref
Rahnert JA, Luo Q, Balog EM, Sokoloff AJ, Burkholder TJ. Changes in growth-related kinases in head, neck and limb muscles with age. Exp Gerontol 2011;46:282-91. PMID: 10.1016/j.exger.2010.11.004. PMID: 21095226.
TOOLS
Share :
Facebook Twitter Linked In Google+ Line it
METRICS Graph View
  • 9 Crossref
  •     Scopus
  • 2,576 View
  • 22 Download
Related articles in Phys Act Nutr


ABOUT
ARTICLE CATEGORY

Browse all articles >

BROWSE ARTICLES
EDITORIAL POLICY
FOR CONTRIBUTORS
Editorial Office
Korea University, 145 Anam-Ro, Seongbuk-gu,Seoul 02841, Republic of Korea
Tel: +82-10-2235-0018    Fax: +82-2-3290-2315    E-mail: jenbedit@gmail.com                

Copyright © 2024 by Korean Society for Exercise Nutrition.

Developed in M2PI

Close layer
prev next