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Fucoxanthinol attenuates oxidative stress-induced atrophy and loss in myotubes and reduces the triacylglycerol content in mature adipocytes

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Abstract

The combination of sarcopenia and obesity (i.e., sarcopenic obesity) is more strongly associated with disability and metabolic/cardiovascular diseases than obesity or sarcopenia alone. Therefore, countermeasures that simultaneously suppress fat gain and muscle atrophy to prevent an increase in sarcopenic obesity are warranted. The aim of this study was to investigate the simultaneous effects of fucoxanthinol (FXOH) on fat loss in mature adipocytes and the inhibition of atrophy and loss in myotubes induced by oxidative stress. C2C12 myotubes were treated with FXOH for 24 h and further incubated with hydrogen peroxide (H2O2) for 24 h. The area of myosin heavy chain-positive myotubes and the ROS concentration were measured. Mature 3T3-L1 adipocytes were treated with FXOH for 72 h. The triacylglycerol (TG) content and glycerol and fatty acid (FA) release were biochemically measured. The myotube area was smaller in H2O2-treated cells than that in control cells. However, FXOH protected against the H2O2-induced decreases in myotube area. Further, the ROS concentration was significantly higher in the FXOH-treated cells compared with that in the control cells, although it was significantly lower than that in the H2O2-treated cells. On the other hand, in the mature adipocytes, the TG content was significantly decreased by FXOH treatment compared to that in the control. Moreover, FXOH treatment significantly increased glycerol and FA release compared with that of the control. These results suggest that FXOH inhibits H2O2-induced atrophy and loss in myotubes and activates lipolysis and decreases the TG content in mature adipocytes. Accordingly, FXOH has the potential to exert anti-sarcopenic obesity effects.

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References

  1. Roubenoff R (2000) Sarcopenic obesity: does muscle loss cause fat gain? Lessons from rheumatoid arthritis and osteoarthritis. Ann N Y Acad Sci 904:553–557. https://doi.org/10.1111/j.1749-6632.2000.tb06515.x

    Article  CAS  PubMed  Google Scholar 

  2. Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS (2001) Sarcopenia. J Lab Clin Med 137:231–243. https://doi.org/10.1067/mlc.2001.113504

    Article  CAS  PubMed  Google Scholar 

  3. Zamboni M, Mazzali G, Fantin F, Rossi A, Francesco VD (2008) Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis 18:388–395. https://doi.org/10.1016/j.numecd.2007.10.002

    Article  CAS  PubMed  Google Scholar 

  4. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445. https://doi.org/10.1146/annurev-immunol-031210-101322

    Article  CAS  PubMed  Google Scholar 

  5. Kim TN, Yang SJ, Yoo HJ, Lim KI, Kang HJ, Song W, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM (2009) Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study. Int J Obes 33:885–892. https://doi.org/10.1038/ijo.2009.130

    Article  CAS  Google Scholar 

  6. Hashimoto T, Ozaki Y, Taminato M, Das SK, Mizuno M, Yoshimura K, Maoka T, Kanazawa K (2009) The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br J Nutr 102:242–248. https://doi.org/10.1017/s0007114508199007

    Article  CAS  PubMed  Google Scholar 

  7. Hosokawa M, Miyashita T, Nishikawa S, Emi S, Tsukui T, Beppu F, Okada T, Miyashita K (2010) Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic/obese KK-Ay mice. Arch Biochem Biophys 504:17–25. https://doi.org/10.1016/j.abb.2010.05.031

    Article  CAS  PubMed  Google Scholar 

  8. Yim MJ, Hosokawa M, Mizushina Y, Yoshida H, Saito Y, Miyashita K (2011) Suppressive effects of amarouciaxanthin A on 3T3-L1 adipocyte differentiation through down-regulation of PPARgamma and C/EBPalpha mRNA expression. J Agric Food Chem 59:1646–1652. https://doi.org/10.1021/jf103290f

    Article  CAS  PubMed  Google Scholar 

  9. Rebello CJ, Greenway FL, Johnson WD, Ribnicky D, Poulev A, Stadler K, Coulter AA (2017) Fucoxanthin and its metabolite fucoxanthinol do not induce browning in human adipocytes. J Agric Food Chem 65:10915–10924. https://doi.org/10.1021/acs.jafc.7b03931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kang SI, Shin HS, Kim HM, Yoon SA, Kang SW, Kim JH, Ko HC, Kim SJ (2012) Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase. J Agric Food Chem 60:3389–3395. https://doi.org/10.1021/jf2047652

    Article  CAS  PubMed  Google Scholar 

  11. Sheard PW, Anderson RD (2012) Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles. Biogerontology 13:157–167. https://doi.org/10.1007/s10522-011-9365-0

    Article  CAS  PubMed  Google Scholar 

  12. Wilkinson DJ, Piasecki M, Atherton PJ (2018) The age-related loss of skeletal muscle mass and function: measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans. Ageing Res Rev 47:123–132. https://doi.org/10.1016/j.arr.2018.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dirks AJ, Leeuwenburgh C (2005) The role of apoptosis in age-related skeletal muscle atrophy. Sport Med 35:473–483. https://doi.org/10.2165/00007256-200535060-00002

    Article  Google Scholar 

  14. Siu PM, Wang Y, Alway SE (2009) Apoptotic signaling induced by H2O2-mediated oxidative stress in differentiated C2C12 myotubes. Life Sci 84:468–481. https://doi.org/10.1016/j.lfs.2009.01.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Escobedo J, Pucci AM, Koh TJ (2004) HSP25 protects skeletal muscle cells against oxidative stress. Free Radic Biol Med 37:1455–1462. https://doi.org/10.1016/j.freeradbiomed.2004.07.024

    Article  CAS  PubMed  Google Scholar 

  16. Meng S-J, Yu L-J (2010) Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 11:1509–1526. https://doi.org/10.3390/ijms11041509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ogawa M, Kariya Y, Kitakaze T, Yamaji R, Harada N, Sakamoto T, Hosotani K, Nakano Y, Inui H (2013) The preventive effect of beta-carotene on denervation-induced soleus muscle atrophy in mice. Br J Nutr 109:1349–1358. https://doi.org/10.1017/s0007114512003297

    Article  CAS  PubMed  Google Scholar 

  18. Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55:8516–8522. https://doi.org/10.1021/jf071848a

    Article  CAS  PubMed  Google Scholar 

  19. Hashimoto T, Yokokawa T, Endo Y, Iwanaka N, Higashida K, Taguchi S (2013) Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes. Biochem Biophys Res Commun 440:43–49. https://doi.org/10.1016/j.bbrc.2013.09.034

    Article  CAS  PubMed  Google Scholar 

  20. Oishi Y, Tsukamoto H, Yokokawa T, Hirotsu K, Shimazu M, Uchida K, Tomi H, Higashida K, Iwanaka N, Hashimoto T (2015) Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy. J Appl Physiol 118:742–749. https://doi.org/10.1152/japplphysiol.00054.2014

    Article  CAS  PubMed  Google Scholar 

  21. Hwang SY, Kang YJ, Sung B, Kim M, Kim DH, Lee Y, Yoo MA, Kim CM, Chung HY, Kim ND (2015) Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway. Int J Mol Med 36:1073–1080. https://doi.org/10.3892/ijmm.2015.2311

    Article  CAS  PubMed  Google Scholar 

  22. Camperi A, Pin F, Costamagna D, Penna F, Menduina ML, Aversa Z, Zimmers T, Verzaro R, Fittipaldi R, Caretti G, Baccino FM, Muscaritoli M, Costelli P (2017) Vitamin D and VDR in cancer cachexia and muscle regeneration. Oncotarget 8:21778–21793. https://doi.org/10.18632/oncotarget.15583

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sakane H, Akasaki K (2018) The major lysosomal membrane proteins LAMP-1 and LAMP-2 participate in differentiation of C2C12 myoblasts. Biol Pharm Bull 41:1186–1193. https://doi.org/10.1248/bpb.b17-01030

    Article  CAS  PubMed  Google Scholar 

  24. Hashimoto T, Kambara N, Nohara R, Yazawa M, Taguchi S (2004) Expression of MHC-beta and MCT1 in cardiac muscle after exercise training in myocardial-infarcted rats. J Appl Physiol 97:843–851. https://doi.org/10.1152/japplphysiol.01193.2003

    Article  CAS  PubMed  Google Scholar 

  25. Hashimoto T, Segawa H, Okuno M, Kano H, Hamaguchi HO, Haraguchi T, Hiraoka Y, Hasui S, Yamaguchi T, Hirose F, Osumi T (2012) Active involvement of micro-lipid droplets and lipid-droplet-associated proteins in hormone-stimulated lipolysis in adipocytes. J Cell Sci 125:6127–6136. https://doi.org/10.1242/jcs.113084

    Article  CAS  PubMed  Google Scholar 

  26. Poljsak B, Suput D, Milisav I (2013) Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev. https://doi.org/10.1155/2013/956792

    Article  PubMed  PubMed Central  Google Scholar 

  27. B. Poljšak, I. Milisav (2013) Aging, oxidative stress and antioxidants. In: JA Morales-González (ed), Oxidative stress and chronic degenerative diseases—a role for antioxidants. IntechOpen. pp 331–356. https://dx.doi.org/10.5772/51609

  28. Shibaguchi T, Yamaguchi Y, Miyaji N, Yoshihara T, Naito H, Goto K, Ohmori D, Yoshioka T, Sugiura T (2016) Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats. Physiol Rep 4:e12885. https://doi.org/10.14814/phy2.12885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nomura T, Kikuchi M, Kubodera A, Kawakami Y (1997) Proton-donative antioxidant activity of fucoxanthin with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Biochem Mol Biol Int 42:361–370. https://doi.org/10.1080/15216549700202761

    Article  CAS  PubMed  Google Scholar 

  30. Pangestuti R, Kim S-K (2011) Neuroprotective effects of marine algae. Mar Drugs 9:803–818. https://doi.org/10.3390/md9050803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang X, Cui YJ, Qi J, Zhu MM, Zhang TL, Cheng M, Liu SM, Wang GC (2018) Fucoxanthin exerts cytoprotective effects against hydrogen peroxide-induced oxidative damage in L02 cells. Biomed Res Int 2018:1085073. https://doi.org/10.1155/2018/1085073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117:399–412. https://doi.org/10.1016/s0092-8674(04)00400-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li YP, Chen Y, Li AS, Reid MB (2003) Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol 285:C806–C812. https://doi.org/10.1152/ajpcell.00129.2003

    Article  CAS  PubMed  Google Scholar 

  34. Servais S, Letexier D, Favier R, Duchamp C, Desplanches D (2007) Prevention of unloading-induced atrophy by vitamin E supplementation: links between oxidative stress and soleus muscle proteolysis? Free Radic Biol Med 42:627–635. https://doi.org/10.1016/j.freeradbiomed.2006.12.001

    Article  CAS  PubMed  Google Scholar 

  35. Haramizu S, Asano S, Butler DC, Stanton DA, Hajira A, Mohamed JS, Alway SE (2017) Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts. J Nutr Biochem 50:103–115. https://doi.org/10.1016/j.jnutbio.2017.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu L, Cash TP, Jones RG, Keith B, Thompson CB, Simon MC (2006) Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 21:521–531. https://doi.org/10.1016/j.molcel.2006.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hardie DG (2008) AMPK and raptor: matching cell growth to energy supply. Mol Cell 30:263–265. https://doi.org/10.1016/j.molcel.2008.04.012

    Article  CAS  PubMed  Google Scholar 

  38. Maeda H, Hosokawa M, Sashima T, Takahashi N, Kawada T, Miyashita K (2006) Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Int J Mol Med 18:147–152. https://doi.org/10.3892/ijmm.18.1.147

    Article  CAS  PubMed  Google Scholar 

  39. Hashimoto T, Sato K, Iemitsu M (2013) Exercise-inducible factors to activate lipolysis in adipocytes. J Appl Physiol 1985(115):260–267. https://doi.org/10.1152/japplphysiol.00427.2013

    Article  CAS  Google Scholar 

  40. Wakil SJ, Abu-Elheiga LA (2009) Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 50:S138–S143. https://doi.org/10.1194/jlr.R800079-JLR200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lodhi IJ, Yin L, Jensen-Urstad AP, Funai K, Coleman T, Baird JH, El Ramahi MK, Razani B, Song H, Fu-Hsu F, Turk J, Semenkovich CF (2012) Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity. Cell Metab 16:189–201. https://doi.org/10.1016/j.cmet.2012.06.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Viollet B, Andreelli F (2011) AMP-activated protein kinase and metabolic control. Handb Exp Pharmacol. https://doi.org/10.1007/978-3-642-17214-4_13

    Article  PubMed  PubMed Central  Google Scholar 

  43. Narkar VA, Downes M, Yu RT, Embler E, Wang Y-X, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405–415. https://doi.org/10.1016/j.cell.2008.06.051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (#26702029 and #18K19762 to TH) and funding from TOYO INSTITUTE of FOOD TECHNOLOGY.

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Correspondence to Takeshi Hashimoto.

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Yoshikawa, M., Hosokawa, M., Miyashita, K. et al. Fucoxanthinol attenuates oxidative stress-induced atrophy and loss in myotubes and reduces the triacylglycerol content in mature adipocytes. Mol Biol Rep 47, 2703–2711 (2020). https://doi.org/10.1007/s11033-020-05369-8

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