No CrossRef data available.
Article contents
Creatine ameliorates the adverse effects of high-fat diet on hepatic lipid metabolism, intestinal health, muscle growth and flesh quality in juvenile largemouth bass (Micropterus salmoides)
Published online by Cambridge University Press: 16 May 2025
Abstract
With the widespread use of high-fat diets (HFD) in aquaculture, the adverse effects of HFD on farmed fish are becoming increasingly apparent. Creatine has shown potential as a green feed additive in farmed fish; however, the potential of dietary creatine to attenuate adverse effects caused by high-fat diets remains poorly understood. To address such gaps, this study was conducted to investigate the mitigating effect of dietary creatine on HFD-induced disturbance on growth performance, hepatic lipid metabolism, intestinal health and muscle quality of juvenile largemouth bass. Three diets were formulated: a control diet (10·20 % lipid), a high-fat diet (HFD, 18·31 % lipid) and HFD with 2 % creatine (HFD + creatine). Juvenile largemouth bass (3·73 (sem 0·01) g) were randomly assigned to three diets for 10 weeks. The key findings were as follows: (1) the expression of muscle growth-related genes and proteins was stimulated by dietary creatine, which contributes to ameliorate the adverse effects of HFD on growth performance; (2) dietary creatine alleviates HFD-induced adverse effects on intestinal health by improving intestinal health, which also enhances feed utilisation efficiency; (3) dietary creatine causes excessive lipid deposition, mainly via lipolysis and β-oxidation. Notably, this study also reveals a previously undisclosed effect of creatine supplementation on improving muscle quality. Together, for the first time from a comprehensive multiorgan or tissue perspective, our study provides a feasible approach for developing appropriate nutritional strategies to alleviate the adverse effects of HFD on farmed fish, based on creatine supplementation.
Keywords
Information
- Type
- Research Article
- Information
- Copyright
- © The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society
Footnotes
*
These authors contributed equally.
References
Jobling, M (2012) National Research Council (NRC): nutrient requirements of fish and shrimp. Aquacult Int 20, 3.CrossRefGoogle Scholar
Sambra, V, Echeverria, F, Valenzuela, A, et al. (2021) Docosahexaenoic and arachidonic acids as neuroprotective nutrients throughout the life cycle. Nutrients 13, 986.CrossRefGoogle Scholar
Xie, S, Yin, P, Tian, T, et al. (2020) Dietary supplementation of Astaxanthin improved the growth performance, antioxidant ability and immune response of juvenile largemouth bass (Micropterus salmoides) fed high-fat diet. Mar Drugs 18, 642.CrossRefGoogle ScholarPubMed
Boujard, T, Gélineau, A, Covès, D, et al. (2003) Regulation of feed intake, growth, nutrient and energy utilisation in European sea bass (Dicentrarchus labrax) fed high fat diets. Aquaculture 231, 529–545.CrossRefGoogle Scholar
Ma, B, Wang, L, Lou, B, et al. (2020) Chen, dietary protein and lipid levels affect the growth performance, intestinal digestive enzyme activities and related genes expression of juvenile small yellow croaker (Larimichthys polyactis). Aquaculture 17, 100403.Google Scholar
Li, P, Song, Z, Huang, L, et al. (2023) Effects of dietary protein and lipid levels in practical formulation on growth, feed utilization, body composition, and serum biochemical parameters of growing rockfish Sebastes schlegeli. Aqua Nutr 2023, 9970252–9970252.CrossRefGoogle ScholarPubMed
Vial, G, Dubouchaud, H, Couturier, K, et al. (2011) Effects of a high-fat diet on energy metabolism and ROS production in rat liver. J Hepatol 54, 348–356.CrossRefGoogle ScholarPubMed
Doré, J & Blottière, H (2015) The influence of diet on the gut microbiota and its consequences for health. Curr Opin Biotech 32, 195–199.CrossRefGoogle ScholarPubMed
Morais, S, Bell, J, Robertson, AD, et al. (2001) Protein/lipid ratios in extruded diets for Atlantic cod (Gadus morhua L.): effects on growth, feed utilisation, muscle composition and liver histology. Aquaculture 203, 101–119.CrossRefGoogle Scholar
Wang, B, Liu, Y, Feng, L, et al. (2015) Effects of dietary arginine supplementation on growth performance, flesh quality, muscle antioxidant capacity and antioxidant-related signalling molecule expression in young grass carp (Ctenopharyngodon idella). Food Chem 167, 91–99.CrossRefGoogle ScholarPubMed
Jia, R, Cao, L, Du, J, et al. (2020) Effects of high-fat diet on antioxidative status, apoptosis and inflammation in liver of tilapia (Oreochromis niloticus) via Nrf2, TLRs and JNK pathways. Fish Shellfish Immunol 104, 391–401.CrossRefGoogle ScholarPubMed
Lu, K, Xu, W, Liu, W, et al. (2014) Association of Mitochondrial Dysfunction with oxidative stress and immune suppression in blunt snout bream Megalobrama amblycephala fed a high-fat diet. Aquat Anim Health 26, 100–112.CrossRefGoogle ScholarPubMed
Lu, KL, Xu, WN, Wang, LN, et al. (2014) Hepatic β-oxidation and regulation of Carnitine Palmitoyltransferase (CPT) I in blunt snout bream Megalobrama amblycephala fed a high fat diet. PLoS One 9, e93135.CrossRefGoogle Scholar
Yin, P, Xie, X, Zhuang, Z, et al. (2021) Chlorogenic acid improves health in juvenile largemouth bass (Micropterus salmoides) fed high-fat diets: involvement of lipid metabolism, antioxidant ability, inflammatory response, and intestinal integrity. Aquaculture 545, 737169.CrossRefGoogle Scholar
Kazak, L, Chouchani, ET, Jedrychowski, MP, et al. (2015) A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 22, 43–55.Google Scholar
Kazak, L & Cohen, P (2020) Creatine metabolism: energy homeostasis, immunity and cancer biology. J Nat Rev Endocrinol 16, 421–436.CrossRefGoogle ScholarPubMed
Borchel, A, Verleih, M, Rebl, A, et al. (2014) Creatine metabolism differs between mammals and rainbow trout (Oncorhynchus mykiss). SpringerPlus 3, 510.CrossRefGoogle ScholarPubMed
Schrama, D, de Magalhães, CR, Cerqueira, M, et al. (2022) Effect of creatine and EDTA supplemented diets on European seabass (Dicentrarchus labrax) allergenicity, fish muscle quality and omics fingerprint. J Comp Biochem Physiol 41, 100941–100941.Google ScholarPubMed
Wardani, WW, Alimuddin, A, Junior, MZ, et al. (2021) Growth performance, robustness against stress, serum insulin, IGF-1 and GLUT4 gene expression of red tilapia (Oreochromis sp.) fed diet containing graded levels of creatine. Aquac Nutr 27, 274–286.CrossRefGoogle Scholar
Michiels, J, Maertens, L, Buyse, J, et al. (2012) Supplementation of guanidinoacetic acid to broiler diets: effects on performance, carcass characteristics, meat quality, and energy metabolism. Poult Sci 91, 402–412.CrossRefGoogle ScholarPubMed
Villasante, A, Ramírez, C, Figueroa Villalobos, E, et al. (2023) Creatine in sustainable fish aquaculture. Rev Fish Sci Aquac 31, 420–451.CrossRefGoogle Scholar
Wyss, M & Kaddurah, DR (2000) Creatine and creatinine metabolism. Physiol Rev 80, 1107–1213.CrossRefGoogle ScholarPubMed
Houten, SM, Watanabe, M & Auwerx, J (2006) Endocrine functions of bile acids. EMBO J 25, 1419–1425.CrossRefGoogle Scholar
Chen, G, Hogstrand, C, Luo, Z, et al. (2017) Dietary zinc addition influenced zinc and lipid deposition in the fore-and mid-intestine of juvenile yellow catfish Pelteobagrus fulvidraco. Br J Nutr 118, 570–579.CrossRefGoogle ScholarPubMed
Chen, G, Song, C, Zhao, T, et al. (2022) Mitochondria-dependent oxidative stress mediates ZnO Nanoparticle (ZnO NP)-induced mitophagy and lipotoxicity in freshwater teleost fish. Environ Sci Technol 56, 2407–2420.CrossRefGoogle ScholarPubMed
Dawood, MAO (2021) Nutritional immunity of fish intestines: important insights for sustainable aquaculture. Rev Aquac 13, 642–663.CrossRefGoogle Scholar
Raˇskovi´c, BS, Stankovi´c, MB, Markovi´c, ZZ, et al. (2011) Histological methods in the assessment of different feed effects on live and intestine of fish. Agr Sci 56, 87–100.CrossRefGoogle Scholar
Saraiva, A, Costa, J, Eiras, JC, et al. (2016) Histological study as indicator of juveniles farmed turbot, Scophthalmus maximus L, health status. Aquaculture 459, 210–215.CrossRefGoogle Scholar
Chatzifotis, S, Panagiotidou, M, Papaioannou, N, et al. (2010) Effect of dietary lipid levels on growth, feed utilization, body composition and serum metabolites of meagre (Argyrosomus regius) juveniles. Aquaculture 307, 65–70.CrossRefGoogle Scholar
Zhou, Y, Guo, J, Tang, R, et al. (2020) High dietary lipid level alters the growth, hepatic metabolism enzyme, and anti-oxidative capacity in juvenile largemouth bass Micropterus salmoides. Fish Physiol Biochem 46, 125–134.CrossRefGoogle ScholarPubMed
Zhang, Y & Edwards, PA (2008) FXR signaling in metabolic disease. FEBS Lett 582, 10–18.CrossRefGoogle ScholarPubMed
Buckingham, M & Rigby, PWJ (2014) Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev Cell 28, 225–238.CrossRefGoogle ScholarPubMed
Johnston, IA, Bower, NI & Macqueen, DJ (2011) Growth and the regulation of myotomal muscle mass in teleost fish. J Exp Biol 214, 1617–1628.CrossRefGoogle ScholarPubMed
Yu, E, Fu, B, Wang, G, et al. (2020) Proteomic and metabolomic basis for improved textural quality in crisp grass carp (Ctenopharyngodon idellus C.et V) fed with a natural dietary pro-oxidant. Food Chem 325, 126906.CrossRefGoogle ScholarPubMed
Zhang, X, Wang, J, Tang, R, et al. (2019) Improvement of muscle quality of grass carp (Ctenopharyngodon idellus) with a bio-floating bed in culture ponds. Front Physiol 10, 683.CrossRefGoogle ScholarPubMed
Burns, FA & Gatlin, MD (2019) Dietary creatine requirement of red drum (Sciaenops ocellatus) and effects of water salinity on responses to creatine supplementation. Aquaculture 506, 320–324.CrossRefGoogle Scholar
Coyle, DS, Tidwell, HJ & Webster, DC (2000) Response of largemouth bass Micropterus salmoides to dietary supplementation of lysine, methionine, and highly unsaturated fatty acids. J World Aquacult Soc 31, 89–95.CrossRefGoogle Scholar
Pei, C, Song, H, Zhu, L, et al. (2021) Identification of Aeromonas veronii isolated from largemouth bass (Micropterus salmoides) and histopathological analysis. Aquaculture 540, 736707.CrossRefGoogle Scholar
Guo, J, Zhou, Y, Zhao, H, et al. (2019) Effect of dietary lipid level on growth, lipid metabolism and oxidative status of largemouth bass, Micropterus salmoides
. Aquaculture 506, 394–400.CrossRefGoogle Scholar
Yin, P, Xie, X, Zhuang, Z, et al. (2021) Dietary supplementation of bile acid attenuate adverse effects of high-fat diet on growth performance, antioxidant ability, lipid accumulation and intestinal health in juvenile largemouth bass (Micropterus salmoides). Aquaculture 531, 735864.CrossRefGoogle Scholar
Yin, P, Xie, S, Huo, Y, et al. (2018) Effects of dietary oxidized fish oil on growth performance, antioxidant defense system, apoptosis and mitochondrial function of juvenile largemouth bass (Micropterus sal moides). Aquaculture 500, 347–358.CrossRefGoogle Scholar
Zhao, T, Lv, WH, Hogstrand, C, et al. (2022) Sirt3-Sod2-mROS-Mediated manganese triggered hepatic mitochondrial dysfunction and lipotoxicity in a freshwater teleost. Environ Sci Technol Jun 21, 8020–8033.CrossRefGoogle Scholar
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Wang, Z, Qiao, F, Zhang, W, et al. (2023) The flesh texture of teleost fish: characteristics and interventional strategies. J Rev Aquacult 16, 508–535.CrossRefGoogle Scholar
Morash, JA, Bureau, PD & McClelland, BG (2008) Effects of dietary fatty acid composition on the regulation of carnitine palmitoyltransferase (CPT) I in rainbow trout (Oncorhynchus mykiss). Com Bioch Phy Part B 152, 85–93.CrossRefGoogle ScholarPubMed
Wei, C, Luo, L, Hogstrand, C, et al. (2018) Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF-1/PPARα and Ca2+/CaMKKβ/AMPK pathways. FASEB J 32, 6666–6680.CrossRefGoogle Scholar
Zhang, X, Shen, Z, Qi, T, et al. (2021) Slight increases in salinity improve muscle quality of grass carp (Ctenopharyngodon idellus). Fishes 6, 7–7.CrossRefGoogle Scholar
Ma, X, Feng, L, Wu, P, et al. (2020) Enhancement of flavor and healthcare substances, mouthfeel parameters and collagen synthesis in the muscle of on-growing grass carp (Ctenopharyngodon idella) fed with graded levels of glutamine. Aquaculture 528, 735486.CrossRefGoogle Scholar
Li, L, Li, J, Ning, L, et al. (2020) Mitochondrial fatty acid β-oxidation inhibition promotes glucose utilization and protein deposition through energy homeostasis remodeling in fish. J Nutr 150, 2322–2335.CrossRefGoogle ScholarPubMed
Adeshina, I & Abdel-Tawwab, M (2021) Dietary creatine enhanced the performance, antioxidant and immunity biomarkers of African catfish, Clarias gariepinus (B.), fed high plant-based diets. Aquac Res 52, 6751–6759.CrossRefGoogle Scholar
Gao, S, Chen, W, Zhang, Y, et al. (2023) Guar gum improves growth performance, intestinal microbiota homeostasis, and hepatic lipid metabolism in juvenilelargemouth bass (Micropterus salmoides) fed high-fat diets. Int J Biol Macrom 235, 123807–123807.CrossRefGoogle Scholar
Perez, ÉS, Duran, BOS, Zanella, BTT, et al. (2023) Review: understanding fish muscle biology in the indeterminate growth species pacu (Piaractus mesopotamicus). Comp Biochem Phys A 285, 111502.CrossRefGoogle ScholarPubMed
Tian, J, Cheng, X, Yu, L, et al. (2022) Role of creatine supplementation on the myofiber characteristics and muscle protein synthesis of grass carp (Ctenopharyngodon idellus). Br J Nutr 130, 41–45.Google Scholar
Lin, J, Liao, Y, Li, X, et al. (2023) Effects of dietary creatine levels on the growth, muscle energy metabolism and meat quality of spotted seabass (Lateolabrax maculatus) fed low–fishmeal diets. Aquaculture 565, 739075.CrossRefGoogle Scholar
Yu, H, He, Y, Qin, M, et al. (2024) Dietary creatine promotes creatine reserves, protein deposition, and myofiber hyperplasia in muscle of juvenile largemouth bass (Micropterus salmoides). Aquaculture 583, 740591.CrossRefGoogle Scholar
Koganti, P, Yao, J & Cleveland, BM (2020) Molecular mechanisms regulating muscle plasticity in fish. Animals 11, 61–61.CrossRefGoogle ScholarPubMed
Liang, X, Cao, C, Chen, P, et al. (2020) Effects of dietary zinc sources and levels on growth performance, tissue zinc retention and antioxidant response of juvenile common carp (Cyprinus carpio var. Jian) fed diets containing phytic acid. Aquacult Nutr 26, 410–421.CrossRefGoogle Scholar
Ling, S, Zhuo, M, Zhang, D, et al. (2020) Nano-Zn increased Zn accumulation and triglyceride content by up-regulating lipogenesis in freshwater teleost, yellow catfish Pelteobagrus fulvidraco. Int J Mol Sci 21, 1615.CrossRefGoogle ScholarPubMed
Lindholm, LP, Koskela, J, Kaseva, J, et al. (2020) Accumulation of geosmin and 2-methylisoborneol in European whitefish Coregonus lavaretus and rainbow trout Oncorhynchus Mykiss in RAS. Fishes 5, 13.CrossRefGoogle Scholar
Eiras, B, Campelo, D, Moura, L, et al. (2022) Feeding rate and frequency during the first feeding of angelfish (Pterophyllum scalare-Schultze, 1823) and severum (Heros severus-Heckel, 1840) with Moina sp. Aquaculture 553, 738106.CrossRefGoogle Scholar
Garcia, MA, Nelson, WJ & Chavez, N (2018) Cell-cell junctions organize structural and signaling networks. Cold Spring Harb Perspect Biol 10, 029181.CrossRefGoogle ScholarPubMed
Xu, J, Jia, B, Zhao, T, et al. (2023) Influences of five dietary manganese sources on growth, feed utilization, lipid metabolism, antioxidant capacity, inflammatory response and endoplasmic reticulum stress in yellow catfish intestine. Aquaculture 566, 739190.CrossRefGoogle Scholar
Fattman, CL, Schaefer, LM & Oury, TD (2003) Extracellular superoxide dismutase in biology and medicine. Free Radic Biol Med 35, 236–256.CrossRefGoogle ScholarPubMed
Zhao, X, Chen, W, Zhang, Y, et al. (2024) Dietary guar gum supplementation reduces the adverse effects of high-fat diets on the growth performance, antioxidant capacity, inflammation, and apoptosis of juvenile largemouth bass (Micropterus salmoides). Anim Feed Sci Tech 308, 115881.CrossRefGoogle Scholar
Chen, YJ, Jiang, YB, Cui, TY, et al. (2023) Creatine ameliorates high-fat diet-induced obesity by regulation of lipolysis and lipophagy in brown adipose tissue and liver. Biochimie 209, 85–94.CrossRefGoogle Scholar
Du, H, Lv, H, Xu, Z, et al. (2020) The mechanism for improving the flesh quality of grass carp (Ctenopharyngodon idella) following the micro-flowing water treatment using a UPLC-QTOF/MS based metabolomics method. Food Chem 327, 126777.CrossRefGoogle ScholarPubMed
Liyana, PC, Shahidi, F, Whittick, A, et al. (2002) Effect of season and artificial diet on amino acids and nucleic acids in gonads of green sea urchin Strongylocentrotus droebachiensis. Comp Biochem Physiol Part A Mol Integr Physiol 133, 389–398.CrossRefGoogle Scholar
Borchel, A, Verleih, M, Rebl, A, et al. (2014) Creatine metabolism differs between mammals and rainbow trout (Oncorhynchus mykiss). SpringerPlus 3, 510.CrossRefGoogle ScholarPubMed
Wang, L, Chen, D, Yang, L, et al. (2010) Expression patterns of the creatine metabolism-related molecules AGAT, GAMT and CT1 in adult zebrafish Danio rerio. Fish Biol 76, 1212–1219.CrossRefGoogle ScholarPubMed
Borchel, A, Verleih, M, Kühn, C, et al. (2019) Goldammer, evolutionary expression differences of creatine synthesis-related genes: implications for skeletal muscle metabolism in fish. Sci Rep 9, 1–8.CrossRefGoogle ScholarPubMed
Zhang, H, Xiong, S & Yu, X (2023) An Yueqi. Fishy odorants in pre-processed fish fillet and surimi products made from freshwater fish: formation mechanism and control methods. Trends Food Sci Tech 142, 104212.CrossRefGoogle Scholar
Song et al. supplementary material
Song et al. supplementary material
File
45.2 KB