Skeletal muscles are important for body movement, postural maintenance, and energy metabolism. Muscle atrophy is caused by various factors, including lack of exercise, age, genetics, and malnutrition, leading to the loss of muscle mass. The Akt/FoxO signaling pathway plays a key role in the regulation of muscle protein synthesis and degradation. Whole wheat contains functional ingredients that may indirectly contribute to muscle health and function and can help prevent or slow the progression of muscle atrophy. In this study, the protective effects of three wheat cultivars (Seodun, Ol, and Shinmichal 1) against hydrogen peroxide-induced muscle atrophy in C2C12 cells were investigated. We found that whole-wheat treatment reduced reactive oxygen species production, prevented glutathione depletion, and increased myotube diameter, thereby reducing muscle atrophy by activating myoblast differentiation. Generally, “Shinmichal 1” exhibited the highest activation of the Akt/FoxO signaling pathway. In contrast, “Seodun” showed similar or slightly higher activities than those of the H2O2-treated only group. In conclusion, whole wheat exerts a protective effect against muscle atrophy by activating the Akt/FoxO signaling pathway. This study indicates that whole wheat may help prevent muscle atrophy.
Get full access to this article
View all access options for this article.
References
1.
HargreavesM, SprietLL. Skeletal muscle energy metabolism during exercise. Nat Metab, 2020; 2(9):817–828; doi: 10.1038/s42255-020-00290-7
2.
BennellKL, WrigleyTV, HuntMA, et al.Update on the role of muscle in the genesis and management of knee osteoarthritis. Rheum Dis Clin North Am, 2013; 39(1):145–176; doi: 10.1016/j.rdc.2012.11.003
3.
MizgierML, CasasM, Contreras FerratA, et al.Potential role of skeletal muscle glucose metabolism on the regulation of insulin secretion. Obes Rev, 2014; 15(7):587–597; doi: 10.1111/obr.12166
4.
JensenJ, RustadPI, KolnesAJ, et al.The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise. Front Physiol, 2011; 2:112; doi: 10.3389/fphys.2011.00112
5.
McGregorRA, Cameron SmithD, PoppittSD. It is not just muscle mass: A review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev Healthspan, 2014; 3:1–8; doi: 10.1186/2046-2395-3-9
6.
SchiaffinoS, DyarKA, CiciliotS, et al.Mechanisms regulating skeletal muscle growth and atrophy. FEBS J, 2013; 280(17):4294–4314; doi: 10.1111/febs.12253
7.
CurtisE, LitwicA, CooperC, et al.Determinants of muscle and bone aging. J Cell Physiol, 2015; 230(11):2618–2625; doi: 10.1002/jcp.25001
HortobágyiT, DempseyL, FraserD, et al.Changes in muscle strength, muscle fibre size and myofibrillar gene expression after immobilization and retraining in humans. J Physiol, 2000; 524(1):293–304; doi: 10.1111/j.1469-7793.2000.00293.x
10.
EleyHL, TisdaleMJ. Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. J Biol Chem, 2007; 282(10):7087–7097; doi: 10.1074/jbc.M610378200
11.
PhilippouA, HalapasA, MaridakiM, et al.Type I insulin-like growth factor receptor signaling in skeletal muscle regeneration and hypertrophy. J Musculoskelet Neuronal Interact, 2007; 7(3):208–218.
12.
HajduchE, BalendranA, BattyI, et al.Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells. Diabetologia, 2001; 44:173–183; doi: 10.1007/s001250051596
13.
OrtegaMA, Fraile MartínezO, Asúnsolo Á, et al. Signal transduction pathways in breast cancer: The important role of PI3K/Akt/mTOR. J Oncol, 2020; 2020; doi: 10.1155/2020/9258396
14.
TimmermanKL, LeeJL, DreyerHC, et al.Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab, 2010; 95(8):3848–3857; doi: 10.1210/jc.2009-2696
15.
YamagataK, DaitokuH, TakahashiY, et al.Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol Cell, 2008; 32(2):221–231; doi: 10.1016/j.molcel.2008.09.013
16.
BodineSC, BaehrLM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab, 2014; 307(6):E469–E484; doi: 10.1152/ajpendo.00204.2014
17.
WangY, LiuQ, QuanH, et al.Nutraceuticals in the prevention and treatment of the muscle atrophy. Nutrients, 2021; 13(6):1914; doi: 10.3390/nu13061914
18.
SidhuJS, KabirY, HuffmanFG. Functional foods from cereal grains. Int J Food Prop, 2007; 10(2):231–244; doi: 10.1080/10942910601045289
19.
LuthriaDL, LuY, JohnKM. Bioactive phytochemicals in wheat: Extraction, analysis, processing, and functional properties. J Funct Food, 2015; 18:910–925; doi: 10.1016/j.jff.2015.01.001
20.
KumarP, YadavaR, GollenB, et al.Nutritional contents and medicinal properties of wheat: A review. Life Sci Med Res, 2011; 22(1):1–10.
21.
AwikaJM, RoseDJ, SimsekS. Complementary effects of cereal and pulse polyphenols and dietary fiber on chronic inflammation and gut health. Food Funct, 2018; 9(3):1389–1409; doi: 10.1039/C7FO02011B
22.
PowersSK, LynchGS, MurphyKT, et al.Disease-induced skeletal muscle atrophy and fatigue. Med Sci Sports Exerc, 2016; 48(11):2307; doi: 10.1249/MSS.0000000000000975
LeeaV. Cholesterol and skeletal muscle health. World Rev Nutr Diet, 2009; 100:71–77; doi: 10.1159/000235713
25.
WaltzTB, FivensonEM, MorevatiM, et al.Sarcopenia, aging and prospective interventional strategies. Curr Med Chem, 2018; 25(40):5588–5596; doi: 10.2174/0929867324666170801095850
26.
HeoH, LeeH, ParkJ, et al.Antioxidant and cytoprotective capacities of various wheat (Triticum aestivum L.) cultivars in Korea. Foods, 2022; 11(15):2338; doi: 10.3390/foods11152338
27.
ChenC, YangJS, LuCC, et al.Effect of quercetin on dexamethasone-induced C2C12 skeletal muscle cell injury. Molecules, 2020; 25(14):3267; doi: 10.3390/foods11152338
28.
OtsukaY, EgawaK, KanzakiN, et al.Quercetin glycosides prevent dexamethasone-induced muscle atrophy in mice. Biochem Biophys Rep, 2019; 18:100618; doi: 10.1016/j.bbrep.2019.100618
29.
Van MeerlooJ, KaspersGJ, CloosJ. Cell sensitivity assays: The MTT assay. In: Cancer cell culture: methods and protocols, 2011; pp. 237–245; doi: 10.1007/978-1-61779-080-5_20
30.
EruslanovE, KusmartsevS. Identification of ROS using oxidized DCFDA and flow-cytometry. In: Advanced Protocols in Oxidative Stress II, 2010; pp. 57–72; doi: 10.1007/978-1-60761-411-1_4
31.
BakerMA, CernigliaGJ, ZamanA. Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. Anal Biochem, 1990; 190(2):360–365; doi: 10.1016/0003-2697(90)90208-q
StevensonEJ, KoncarevicA, GiresiPG, et al.Transcriptional profile of a myotube starvation model of atrophy. J Appl Physiol, 2005; 98(4):1396–1406; doi: 10.1152/japplphysiol.01202.2006
34.
WangM, HuR, WangY, et al.Atractylenolide III attenuates muscle wasting in chronic kidney disease via the oxidative stress-mediated PI3K/AKT/mTOR pathway. Oxidative Med Cell Longev, 2019; 2019; doi: 10.1155/2019/1875471
35.
PowersSK, SmuderA, JudgeA. Oxidative stress and disuse muscle atrophy: Cause or consequence?. Curr Opin Clin Nutr Metab Care, 2012; 15(3):240; doi: 10.1097/MCO.0b013e328352b4c2
36.
KondoH, KodamaJ, KishibeT, et al.Oxidative stress during recovery from muscle atrophy. FEBS Lett, 1993; 326(1–3):189–191; doi: 10.1016/0014-5793(93)81788-2
37.
BajajP, Reddy JrB, MilletL, et al.Patterning the differentiation of C2C12 skeletal myoblasts. Integr Biol, 2011; 3(9):897–909; doi: 10.1039/c1ib00058f
38.
MilewskaM, GrabiecK, Grzelkowska-KowalczykK. Interactions of proliferation and differentiation signaling pathways in myogenesis. Adv Hygiene Exp Med, 2014; 68:517–527; doi: 10.5604/17322693.1101617
39.
EomYW, LeeJE, YangMS, et al.Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts. Biochem Biophys Res Commun, 2011; 408(1):167–173; doi: 10.1016/j.bbrc.2011.04.002
40.
DeschenesMR. Effects of aging on muscle fibre type and size. Sports Med, 2004; 34:809–824; doi: 10.2165/00007256-200434120-00002
41.
LeeS, KimMB, KimC, et al.Whole grain cereal attenuates obesity-induced muscle atrophy by activating the PI3K/Akt pathway in obese C57BL/6N mice. Food Sci Biotechnol, 2018; 27:159–168; doi: 10.1007/s10068-017-0277-x
42.
KimC, LeeJ, KimMB, et al.Hypoglycemic effect of whole grain diet in C57BL/KsJ-db/db mice by activating PI3K/Akt and AMPK pathways. Food Sci Biotechnol, 2019; 28:895–905; doi: 10.1007/s10068-018-0533-8
43.
HahYS, LeeWK, LeeS, et al.β-Sitosterol attenuates dexamethasone-induced muscle atrophy via regulating FoxO1-dependent signaling in C2C12 cell and mice model. Nutrients, 2022; 14(14):2894; doi: 10.3390/nu14142894
44.
HiramotoS, YahataN, SaitohK, et al.Dietary supplementation with alkylresorcinols prevents muscle atrophy through a shift of energy supply. J Nutr Biochem, 2018; 61:147–154; doi: 10.1016/j.jnutbio.2018.08.014
