Effects of Byproduct Lactic Acid and Byproduct Betaine As Feed Additives on the Metabolomic Profiles of Blood, Meat, and Fat Tissue of Juvenile Bester Sturgeon (Acipenser ruthenus × Huso huso)

Qi Liu¹, Takeshi Naganuma^1, , Akio Ueno², Shuji Tamamura² and Takuma Murakami²

¹Graduate School of Integrated Sciences for Life, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, 739-8528, Japan

²Horonobe Research Institute for the Subsurface Environment, Northern Advancement Center for Science & Technology, 5-3 Sakaemachi, Horonobe-cho, Hokkaido, 098-3221, Japan

Cite this paper:
Qi Liu, Takeshi Naganuma, Akio Ueno, Shuji Tamamura and Takuma Murakami. Effects of Byproduct Lactic Acid and Byproduct Betaine As Feed Additives on the Metabolomic Profiles of Blood, Meat, and Fat Tissue of Juvenile Bester Sturgeon (Acipenser ruthenus × Huso huso). Journal of Food and Nutrition Research. 2025; 13(3):146-155. doi: 10.12691/jfnr-13-3-4

Abstract

The sturgeon is an ancient fish that grows slowly and matures sexually late. The diversity of chromosome numbers makes the biological study of sturgeon difficult. However, as an important aquaculture resource, the exploration of its culture conditions deserves in-depth study. This study reports the metabolomic profiles of the bester sturgeon's blood, meat, and fat when two food industrial byproducts rich in lactic acid and betaine (N,N,N-trimethylglycine), respectively, were used as feed additives using the metabolomic research method. The metabolomic results showed that a total of 388 metabolites were detected, of which 348 metabolites were classified and annotated in the Human Metabolome Database. The differential analysis showed that there were significant differences in the metabolomic profiles among blood, meat, and fat tissues. Screening of differential biomarker metabolites revealed that the main differential biomarker metabolites were derived from blood and that there were differences in the types of differential biomarker metabolites due to the two byproducts. This study provides new insights into the potential use of food industrial byproducts as feed additives and provides a theoretical basis for the improvement of sturgeon culture feeds.

Keywords:
metabolome targeted metabolomics metabolism hybrid sturgeon

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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References:

[1]	Subasinghe, R., Soto, D. and Jia, J., “Global aquaculture and its role in sustainable development,” Reviews in Aquaculture, 1(1), 2-9, Feb 2009.
[2]	Dawood, M.A.O., Habotta, O.A.E., Elsabagh, M., Azra, M. N., Van Doan, H., Kari, Z.A. and Sewilam, H., “Fruit processing byproducts in the aquafeed industry: A feasible strategy for aquaculture sustainability,” Reviews in Aquaculture, 14(4), 1945-1965, May 2022.
[3]	Dawood, M.A.O., Koshio, S. and Esteban, M.Á., “Beneficial roles of feed additives as immunostimulants in aquaculture: a review,” Reviews in Aquaculture, 10(4), 950-974, Dec 2018.
[4]	Vlaicu, P.A., Untea, A.E., Varzaru, I., Saracila, M. and Oancea, A.G., “Designing nutrition for health—incorporating dietary byproducts into poultry feeds to create functional foods with insights into health benefits, risks, bioactive compounds, food component functionality, and safety regulations. Foods, 12(21), Nov 2023.
[5]	Reddy, G., Altaf, M., Naveena, B.J., Venkateshwar, M. and Kumar, E.V., “Amylolytic bacterial lactic acid fermentation — A review,” Biotechnology Advances, 26(1), 22-34, Feb 2008.
[6]	Dobrijević, D., Pastor, K., Nastić, N., Özogul, F., Krulj, J., Kokić, B., Bartkiene, E., Rocha, J.M. and Kojić, J., “Betaine as a functional ingredient: metabolism, health-promoting attributes, food sources, applications and analysis methods,” Molecules, 28(12), Jun 2023.
[7]	Lim, L.S., Chor, W.K., Tuzan, A.D., Shapawi, R. and Kawamura, G., “Betaine is a feed enhancer for juvenile grouper (Epinephelus fuscoguttatus) as determined behaviourally,” Journal of Applied Animal Research, 44(1), 415-418, Oct 2015.
[8]	Pessione, E., “Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows,” Frontiers in Cellular and Infection Microbiology, 2, Jun 2012.
[9]	Mugwanya, M., Dawood, M.A.O., Kimera, F. and Sewilam, H., “A meta-analysis on the influence of dietary betaine on the growth performance and feed utilization in aquatic animals,” Aquaculture Reports, 37, 102200, Jun 2024.
[10]	Liu, Q. and Naganuma, T., “Metabolomics in sturgeon research: a mini-review,” Fish Physiology and Biochemistry, 50 (4), 1895-1910, Aug 2008.
[11]	Pfleger, M.O., Rider, S.J., Johnston, C.E. and Janosik, A.M., “Saving the doomed: Using eDNA to aid in detection of rare sturgeon for conservation (Acipenseridae),” Global Ecology and Conservation, 8, 99-107, Oct 2016.
[12]	Wang, J.H., Byun, J. and Pennathur, S., “Analytical approaches to metabolomics and applications to systems biology,” Seminars in Nephrology, 30(5), 500-511, Sep 2010.
[13]	Picó, C., Serra, F., Rodríguez, A.M., Keijer, J. and Palou, A., “Biomarkers of nutrition and health: New tools for new approaches,” Nutrients, 11(5), May 2019.
[14]	Liu, Q. and Naganuma, T., “Effects of lactic acid and betaine as feed additives on metabolomic profiles of juvenile bester sturgeon (Acipenser ruthenus × Huso huso),” Journal of Food and Nutrition Research, 13(1), 18-33, Jun 2025. https:// pubs.sciepub.com/ jfnr/13/1/3.
[15]	Poli, B.M., Parisi, G., Scappini, F. and Zampacavallo, G., “Fish welfare and quality as affected by pre-slaughter and slaughter management,” Aquaculture International, 13 (1), 29-49, Jan 2005.
[16]	Liu, Q. and Naganuma, T., “Tissue-specific biomarker metabolites of meat, fat and egg of Siberian sturgeon,” Journal of Food and Nutrition Research, 12 (1), 1-13, Feb 2024.
[17]	Chang, F., He, S.S. and Dang, C.Y., “Assisted selection of biomarkers by linear discriminant analysis effect size (LEfSe) in Microbiome Data,” JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (183), May 2022.
[18]	Wishart, D.S., Guo, A., Oler, E., Wang, F., Anjum, A., Peters, H., Dizon, R., Sayeeda, Z., Tian, S., Lee, Brian L., Berjanskii, M., Mah, R., Yamamoto, M., Jovel, J., Torres-Calzada, C., Hiebert-Giesbrecht, M., Lui, Vicki W., Varshavi, D., Varshavi, D., Allen, D., Arndt, D., Khetarpal, N., Sivakumaran, A., Harford, K., Sanford, S., Yee, K., Cao, X., Budinski, Z., Liigand, J., Zhang, L., Zheng, J., Mandal, R., Karu, N., Dambrova, M., Schiöth, Helgi B., Greiner, R. and Gautam, V., “HMDB 5.0: the Human Metabolome Database for 2022,” Nucleic Acids Research, 50(D1), D622-D631, Jan 2022.
[19]	Van der Aar, P.J., Molist, F. and van der Klis, J.D., “The central role of intestinal health on the effect of feed additives on feed intake in swine and poultry,” Animal Feed Science and Technology, 233, 64-75, Nov 2017.
[20]	Pandey, A.K., Kumar, P. and Saxena, M.J., “Feed additives in animal health. In R. C. Gupta, A. Srivastava, & R. Lall (Eds.),” Nutraceuticals in Veterinary Medicine (pp. 345-362), Springer International Publishing, May 2019.
[21]	Bai, S.C., Hamidoghli, A. and Bae, J., “7-Feed additives: an overview,” In D. A. Davis (Ed.), Feed and Feeding Practices in Aquaculture (Second Edition) (pp. 195-229), Woodhead Publishing, May 2022.
[22]	López-Pedrouso, M., Lorenzo, J.M., Cantalapiedra, J., Zapata, C., Franco, J.M. and Franco, D, “Chapter five-aquaculture and byproducts: Challenges and opportunities in the use of alternative protein sources and bioactive compounds,” In J. M. Lorenzo & F. J. Barba (Eds.), Advances in Food and Nutrition Research (Vol. 92, pp. 127-185), Academic Press, Jan 2019.
[23]	Holdt, S.L. and Kraan, S., “Bioactive compounds in seaweed: functional food applications and legislation,” Journal of Applied Phycology, 23(3), 543-597, Feb 2011.
[24]	Ajila, C.M., Brar, S.K., Verma, M., Tyagi, R.D., Godbout, S. and Valéro, J.R. “Bio-processing of agro-byproducts to animal feed,” Critical Reviews in Biotechnology, 32(4), 382-400, Mar 2012.
[25]	Torres-Maravilla, E., Parra, M., Maisey, K., Vargas, R.A., Cabezas-Cruz, A., Gonzalez, A., Tello, M. and Bermúdez-Humarán, L.G., “Importance of probiotics in fish aquaculture: Towards the identification and design of novel probiotics,” Microorganisms, 12(3), Mar 2024.
[26]	Kivimäki, M., Bartolomucci, A. and Kawachi, I., “The multiple roles of life stress in metabolic disorders,” Nature Reviews Endocrinology, 19(1), 10-27, Oct 2022.
[27]	Wikoff, W.R., Anfora, A.T., Liu, J., Schultz, P.G., Lesley, S.A., Peters, E.C. and Siuzdak, G., “Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites,” Proceedings of the National Academy of Sciences, 106(10), 3698-3703, Mar 2009.
[28]	Ng, W.K. and Koh, C.B., “The utilization and mode of action of organic acids in the feeds of cultured aquatic animals,” Reviews in Aquaculture, 9(4), 342-368, Dec 2017.
[29]	Yang, M.J., Cheng, Z.X., Jiang, M., Zeng, Z.H., Peng, B., Peng, X.X. and Li, H., “Boosted TCA cycle enhances survival of zebrafish to Vibrio alginolyticus infection,” Virulence, 9(1), 634-644, Feb 2018.
[30]	Ranea-Robles, P. and Houten, S.M., “The biochemistry and physiology of long-chain dicarboxylic acid metabolism,” Biochemical Journal, 480(9), 607-627, May 2023.
[31]	Guzior, D.V. and Quinn, R.A., “Review: microbial transformations of human bile acids,” Microbiome, 9(1), 140, Jun 2021.
[32]	Pietrowska-Borek, M., Dobrogojski, J., Sobieszczuk-Nowicka, E. and Borek, S., “New insight into plant signaling: Extracellular ATP and uncommon nucleotides,” Cells, 9(2), Feb 2020.
[33]	Kaushik, S.J. and Seiliez, I., “Protein and amino acid nutrition and metabolism in fish: current knowledge and future needs,” Aquaculture Research, 41(3), 322-332. Feb 2010.
[34]	Ochs, R.S. and Harris, R.A., “Mechanism for the oleate stimulation of gluconeogenesis from dihydroxyacetone by hepatocytes from fasted rats,” Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 886(1), 40-47, Apr 1986.
[35]	Yoon, D.S., Kim, D.H., Kim, J.H., Sakakura, Y., Hagiwara, A., Park, H.G., Lee, M.C. and Lee, J.S., “Interactions between lipid metabolism and the microbiome in aquatic organisms: A review,” Marine Pollution Bulletin, 207, 116858, Oct 2024.
[36]	Jenkins, B., West, J.A. and Koulman, A., “A review of odd-chain fatty acid metabolism and the role of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) in health and disease,” Molecules, 20(2), 2425-2444, Jan 2015.
[37]	Fagundes, M.A., Yang, S.Y., Eun, J.S., Hall, J.O., Moon, J.O. and Park, J.S., “Influence of supplementing a methionine derivative, N-acetyl-l-methionine, in dairy diets on production and ruminal fermentation by lactating cows during early to mid lactation,” Journal of Dairy Science, 101(8), 7082-7094, Aug 2018.
[38]	Prinville, V., Ohlund, L. and Sleno, L., “Targeted analysis of 46 bile acids to study the effect of acetaminophen in rat by LC-MS/MS,” METABOLITES, 10(1), Jan 2020.
[39]	Copeman, L.A., Parrish, C.C., Brown, J.A. and Harel, M., “Effects of docosahexaenoic, eicosapentaenoic, and arachidonic acids on the early growth, survival, lipid composition and pigmentation of yellowtail flounder (Limanda ferruginea): a live food enrichment experiment,” Aquaculture, 210(1), 285-304, Jul 2002.
[40]	Hui, S., Ghergurovich, J.M., Morscher, R.J., Jang, C., Teng, X., Lu, W., Esparza, L.A., Reya, T., Le, Z., Yanxiang Guo, J., White, E. and Rabinowitz, J.D., “Glucose feeds the TCA cycle via circulating lactate,” Nature, 551(7678), 115-118, Oct 2017.
[41]	Felig, P., “The glucose-alanine cycle,” Metabolism, 22(2), 179-207, Feb 1973.
[42]	Castillo Martinez, F.A., Balciunas, E.M., Salgado, J.M., Domínguez González, J.M., Converti, A. and Oliveira, R.P.d.S., “Lactic acid properties, applications and production: A review,” Trends in Food Science & Technology, 30(1), 70-83, Mar 2013.
[43]	Kwon, Y., “Effect of trans–fatty acids on lipid metabolism: Mechanisms for their adverse health effects,” Food Reviews International, 32(3), 323-339, Mar 2016.
[44]	Srinivasan, S., Torres, A.G. and Ribas de Pouplana, L., “Inosine in biology and disease,” Genes, 12(4), Apr 2021.
[45]	Tanianskii, D.A., Jarzebska, N., Birkenfeld, A.L., O’Sullivan, J.F. and Rodionov, R.N., “Beta-aminoisobutyric acid as a novel regulator of carbohydrate and lipid metabolism. Nutrients, 11(3), Feb 2019.
[46]	Kamei, Y., Hatazawa, Y., Uchitomi, R., Yoshimura, R. and Miura, S., “Regulation of skeletal muscle function by amino acids. Nutrients, 12(1), Jan 2020.
[47]	Kraemer, W.J. and Volek, J.S. “CREATINE SUPPLEMENTATION: Its role in human performance,” Clinics in Sports Medicine, 18(3), 651-666, Jul 1999.
[48]	Dzeja, P. and Terzic, A., “Adenylate kinase and AMP signaling networks: Metabolic monitoring, signal communication and body energy sensing,” International Journal of Molecular Sciences, 10(4), 1729-1772, Apr 2009.
[49]	Gruzman, A., Babai, G. and Sasson, S., “Adenosine monophosphate-activated protein kinase (AMPK) as a new target for antidiabetic drugs: A review on metabolic, pharmacological and chemical considerations,” Rev Diabet Stud, 6(1), 13-36, May 2009.