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Molecular weight‐dependent effects of Undaria pinnatifida fucoidan isolates on palmitate‐induced inflammation and muscle atrophy in C2C12 myotubes

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Abstract

Obesity is consistently linked to skeletal muscle atrophy. It is characterized by a chronic inflammatory state that produces various pro-inflammatory substances that may have negative effects on muscles, such as muscle atrophy, impaired muscle regeneration, and a reduction in muscle protein synthesis. Fucoidan, isolated from the brown alga Undaria pinnatifida, is composed of fucose, galactose, and sulfate groups, and is known to have anti-obesity, anti-tumor, and immunomodulatory properties. Recent studies have indicated that the bioactivity of fucoidans depends on their molecular weight; however, this correlation remains unclear and requires further investigation. This study aimed to evaluate and compare the effects of three different fucoidans, based on their molecular weight, on palmitate (PA)-induced muscle atrophy using C2C12 myotubes. The fucoidan types were low molecular weight fucoidan (LMWF, ≥ 30 kDa), medium molecular weight fucoidan (MMWF, ≥ 110 kDa), and high molecular weight fucoidan (HMWF, ≥ 200 kDa). Our results demonstrate that all fucoidans reduced lipid accumulation. Additionally, all three fucoidans reduced tumor necrosis factor-alpha (TNF‐α) mRNA expression level in PA‐induced inflammation, whereas interleukin-1beta (IL‐1β) and IL‐6 mRNA expression levels were reduced only in the HMWF-treated group. Moreover, MMWF and HMWF significantly reduced the mRNA expression levels of the muscle atrophy genes muscle RING-finger protein-1 (MuRF1) and Atrogin‐1, while LMWF showed no significant effects. In conclusion, HMWF showed more promising outcomes than LMWF and MMWF, suggesting its potential as a therapeutic agent for the treatment of obesity-induced inflammation and muscle atrophy.

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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

References

  • Akhmedov D, Berdeaux R (2013) The effects of obesity on skeletal muscle regeneration. Front Physiol 4:371

    Article  PubMed  PubMed Central  Google Scholar 

  • Álvarez-Viñas M, Flórez-Fernández N, González-Muñoz MJ, Domínguez H (2019) Influence of molecular weight on the properties of Sargassum muticum fucoidan. Algal Res 38:101393

    Article  Google Scholar 

  • Bodine SC, Baehr LM (2014) Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab 307:E469-484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capel F, Cheraiti N, Acquaviva C, Henique C, Bertrand-Michel J, Vianey-Saban C, Prip-Buus C, Morio B (2016) Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes. Biochim Biophys Acta 1861:2000–2010

    Article  CAS  PubMed  Google Scholar 

  • Chen MC, Hsu WL, Hwang PA, Chen YL, Chou TC (2016) Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice. Oncotarget 7:51608–51618

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi JI, Kim HJ (2013) Preparation of low molecular weight fucoidan by gamma-irradiation and its anticancer activity. Carbohydr Polym 97:358–362

  • Choi WH, Son HJ, Jang YJ, Ahn J, Jung CH, Ha TY (2017) Apigenin ameliorates the obesity-induced skeletal muscle atrophy by attenuating mitochondrial dysfunction in the muscle of obese mice. Mol Nutr Food Res 61:1700218

  • Fitton JH, Dell’Acqua G, Gardiner V-A, Karpiniec SS, Stringer DN, Davis E (2015) Topical benefits of two fucoidan-rich extracts from marine macroalgae. Cosmetics 2:66–81

    Article  CAS  Google Scholar 

  • Gumucio JP, Mendias CL (2013) Atrogin-1, MuRF-1, and sarcopenia. Endocrine 43:12–21

    Article  CAS  PubMed  Google Scholar 

  • Haberecht-Muller S, Kruger E, Fielitz J (2021) Out of control: The role of the ubiquitin proteasome system in skeletal muscle during inflammation. Biomolecules 11:1327

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang CY, Kuo CH, Lee CH (2018) Antibacterial and antioxidant capacities and attenuation of lipid accumulation in 3T3-L1 adipocytes by low-molecular-weight fucoidans prepared from compressional-puffing-pretreated Sargassum crassifolium. Mar Drugs 16:24

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang J, Huang J, Li Y, Lv H, Yin T, Fan S, Zhang C, Li H (2021) Fucoidan protects against high-fat diet-induced obesity and modulates gut microbiota in institute of cancer research mice. J Med Food 24:1058–1067

    Article  CAS  PubMed  Google Scholar 

  • Huynh FK, Green MF, Koves TR, Hirschey MD (2014) Measurement of fatty acid oxidation rates in animal tissues and cell lines. Meth Enzymol 542:391–405

    Article  CAS  Google Scholar 

  • Jayawardena TU, Nagahawatta D, Lu Y-A, Yang H-W, Je J-G, Kim S-Y, Jeon Y-J (2021) Ishige okamurae and diphloroethohydoxycarmalol inhibit palmitic acid-impaired skeletal myogenesis and improve muscle regenerative potential. J Funct Foods 87:104832

    Article  CAS  Google Scholar 

  • Jayawardena TU, Nagahawatta DP, Fernando IPS, Kim YT, Kim JS, Kim WS, Lee JS, Jeon YJ (2022) A review on fucoidan structure, extraction techniques, and its role as an immunomodulatory agent. Mar Drugs 20:755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji Y, Li M, Chang M, Liu R, Qiu J, Wang K, Deng C, Shen Y, Zhu J, Wang W, Xu L, Sun H (2022) Inflammation: Roles in skeletal muscle atrophy. Antioxidants 11:1686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jun L, Robinson M, Geetha T, Broderick TL, Babu JR (2023) Prevalence and mechanisms of skeletal muscle atrophy in metabolic conditions. Int J Mol Sci 24:2973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim KJ, Lee BY (2012) Fucoidan from the sporophyll of Undaria pinnatifida suppresses adipocyte differentiation by inhibition of inflammation-related cytokines in 3T3-L1 cells. Nutr Res 32:439–447

    Article  CAS  PubMed  Google Scholar 

  • Kim KJ, Yoon KY, Lee BY (2012) Low molecular weight fucoidan from the sporophyll of Undaria pinnatifida suppresses inflammation by promoting the inhibition of mitogen-activated protein kinases and oxidative stress in RAW264.7 cells. Fitoterapia 83:1628–1635

  • Le NH, Kim CS, Park T, Park JH, Sung MK, Lee DG, Hong SM, Choe SY, Goto T, Kawada T, Yu R (2014) Quercetin protects against obesity-induced skeletal muscle inflammation and atrophy. Mediators Inflamm 2014:834294

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee K, Jin H, Chei S, Oh HJ, Lee JY, Lee BY (2020) Effect of dietary silk peptide on obesity, hyperglycemia, and skeletal muscle regeneration in high-fat diet-fed mice. Cells 9:377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SH, Ko CI, Ahn G, You S, Kim JS, Heu MS, Kim J, Jee Y, Jeon YJ (2012) Molecular characteristics and anti-inflammatory activity of the fucoidan extracted from Ecklonia cava. Carbohydr Polym 89:599–606

    Article  CAS  PubMed  Google Scholar 

  • Li X, Li J, Li Z, Sang Y, Niu Y, Zhang Q, Ding H, Yin S (2016) Fucoidan from Undaria pinnatifida prevents vascular dysfunction through PI3K/Akt/eNOS-dependent mechanisms in the l-NAME-induced hypertensive rat model. Food Funct 7:2398–2408

    Article  CAS  PubMed  Google Scholar 

  • Lim JM, Yoo HJ, Lee KW (2022) High molecular weight fucoidan restores intestinal integrity by regulating inflammation and tight junction loss induced by methylglyoxal-derived hydroimidazolone-1. Mar Drugs 20:580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu SH, Chiu CY, Wang LP, Chiang MT (2019) Omega-3 fatty acids-enriched fish oil activates AMPK/PGC-1α signaling and prevents obesity-related skeletal muscle wasting. Mar Drugs 17:380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Xu Z, Huang H, Xue Y, Zhang D, Zhang Y, Li W, Li X (2022) Fucoidan ameliorates glucose metabolism by the improvement of intestinal barrier and inflammatory damage in type 2 diabetic rats. Int J Biol Macromol 201:616–629

    Article  CAS  PubMed  Google Scholar 

  • Luthuli S, Wu S, Cheng Y, Zheng X, Wu M, Tong H (2019) Therapeutic effects of fucoidan: A Review on recent studies. Mar Drugs 17:487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mankhong S, Kim S, Moon S, Kwak HB, Park DH, Kang JH (2020) Experimental models of sarcopenia: Bridging molecular mechanism and therapeutic strategy. Cells 9:1385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuba I, Fujita R, Iida K (2023) Palmitic acid inhibits myogenic activity and expression of myosin heavy chain MHC IIb in muscle cells through phosphorylation-dependent MyoD inactivation. Int J Mol Sci 24:5847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McBean SE, Church JE, Thompson BK, Taylor CJ, Fitton JH, Stringer DN, Karpiniec SS, Park AY, van der Poel C (2021) Oral fucoidan improves muscle size and strength in mice. Physiol Rep 9:e14730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park E-J, Choi J-i (2017) Melanogenesis inhibitory effect of low molecular weight fucoidan from Undaria pinnatifida. J Appl Phycol 29:2213–2217

    Article  CAS  Google Scholar 

  • Sadeghi A, Seyyed Ebrahimi SS, Golestani A, Meshkani R (2017) Resveratrol ameliorates palmitate-induced inflammation in skeletal muscle cells by attenuating oxidative stress and JNK/NF-κB pathway in a SIRT1-independent mechanism. J Cell Biochem 118:2654–2663

    Article  CAS  PubMed  Google Scholar 

  • Spate U, Schulze PC (2004) Proinflammatory cytokines and skeletal muscle. Curr Opin Clin Nutr Metab Care 7:265–269

    Article  PubMed  Google Scholar 

  • Tardif N, Salles J, Guillet C, Tordjman J, Reggio S, Landrier JF, Giraudet C, Patrac V, Bertrand-Michel J, Migne C, Collin ML, Chardigny JM, Boirie Y, Walrand S (2014) Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2α activation. Aging Cell 13:1001–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Ai C, Wen C, Qin Y, Liu Z, Wang L, Gong Y, Su C, Wang Z, Song S (2020) Fucoidan isolated from Ascophyllum nodosum alleviates gut microbiota dysbiosis and colonic inflammation in antibiotic-treated mice. Food Funct 11:5595–5606

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Wang L, Yan C, Fu Y, Yang JF, Ma J, Song S (2023) Structural characterization of a fucoidan from Ascophyllum nodosum and comparison of its protective effect against cellular oxidative stress with its analogues. Int J Biol Macromol 239:124295

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Xing M, Cao Q, Ji A, Liang H, Song S (2019) Biological activities of fucoidan and the factors mediating its therapeutic effects: A review of recent studies. Mar Drugs 17:183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Ballantyne CM (2017) Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest 127:43–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang C, Chung D, Shin IS, Lee H, Kim J, Lee Y, You S (2008) Effects of molecular weight and hydrolysis conditions on anticancer activity of fucoidans from sporophyll of Undaria pinnatifida. Int J Biol Macromol 43:433–437

    Article  CAS  PubMed  Google Scholar 

  • Yoo HJ, You DJ, Lee KW (2019) Characterization and immunomodulatory effects of high molecular weight fucoidan fraction from the sporophyll of Undaria pinnatifida in cyclophosphamide-induced immunosuppressed mice. Mar Drugs 17:447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Li Q, Wu J, Yang X, Yang S, Zhu W, Liu Y, Tang W, Nie S, Hassouna A, White WL, Zhao Y, Lu J (2021) Fucoidan extracted from sporophyll of Undaria pinnatifida grown in Weihai, China - Chemical composition and comparison of antioxidant activity of different molecular weight fractions. Front Nutr 8:636930

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Zheng Y, Wang J, Ma S, Yu Y, White WL, Yang S, Yang F, Lu J (2018) Fucoidan extracted from Undaria pinnatifida: Source for nutraceuticals/functional foods. Mar Drugs 16:321

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuo J, Zhang Y, Wu Y, Liu J, Wu Q, Shen Y, Jin L, Wu M, Ma Z, Tong H (2022) Sargassum fusiforme fucoidan ameliorates diet-induced obesity through enhancing thermogenesis of adipose tissues and modulating gut microbiota. Int J Biol Macromol 216:728–740

    Article  CAS  PubMed  Google Scholar 

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Funding

This research was supported by Korea Institute of Marine Science & Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries, Republic of Korea (20220027), and by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through High Value‐Added Food Technology development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA)(grant number 321024‐04‐1‐HD020).

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Jong‐Yeon Kim: Methodology, validation, formal analysis, investigation, visualization, writing ‐ original draft preparation. Eun‐Jung Park: Conceptualization, methodology, formal analysis, visualization, writing ‐ review and editing, supervision, project administration. Hae‐Jeung Lee: Conceptualization, writing ‐ review and editing, supervision, project administration. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Eun‐Jung Park or Hae‐Jeung Lee.

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Kim, J., Park, E. & Lee, H. Molecular weight‐dependent effects of Undaria pinnatifida fucoidan isolates on palmitate‐induced inflammation and muscle atrophy in C2C12 myotubes. J Appl Phycol 36, 411–419 (2024). https://doi.org/10.1007/s10811-023-03111-y

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