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Effects of dietary berberine on growth performance, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus) fed high-fat diets

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Abstract

This study aimed to investigate the effects of high-fat diet (HFD) supplemented with berberine on growth, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus). Five hundred and forty healthy fish (4.04 ± 0.01 g) were randomly distributed into six groups, and fed six experimental diets: normal-fat diet (NFD, 5% fat), HFD (15% fat), and four HFDs supplemented with graded levels of berberine, respectively. The results showed that, compared with fish fed NFD, HFD had no effects on the growth of fish except for reducing survival rate, whereas HFD caused extensive lipid accumulation, oxidative stress injury and hepatic abnormalities. However, compared with the HFD group, fish fed HFD containing an appropriate berberine (98.26 or 196.21 mg/kg) improved the growth performance, increased hepatic lipid metabolism and antioxidant enzymes activities, and up-regulated the mRNA expression levels of ampk subunits and lipolysis genes such as pparα, cpt-1, acox, atgl and hsl (P < 0.05). Meanwhile, HFD supplemented with an appropriate berberine reduced crude lipid contents in liver and whole-body, decreased serum lipid contents, and ALT and AST activities, and down-regulated the mRNA expression levels of lipogenesis genes such as srebp-1, acc1, gpat, fas and pparγ, and lipid transporter genes such as fatp, fabp and fat/cd36 (P < 0.05). Thus, HFD supplemented with an appropriate berberine could improve growth of black carp, promote lipid metabolism and enhance antioxidant capacity. The lipid-lowering mechanism of berberine might be mediated by activating AMPK pathway, up-regulating lipolysis genes expression, and down-regulating lipogenesis and transport genes expression.

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All data used to support the study’s conclusions are contained in this published article; further details can be requested from the corresponding authors.

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Abbreviations

acc1 :

Cetyl-CoA carboxylase 1

acox :

Acyl-coenzyme A oxidase

ALT:

Alanine aminotransferase

AMPK:

AMP-activated protein kinase

AST:

Aspartate aminotransferase

atgl :

Adipose triglyceride lipase

cpt-1 :

Carnitine palmitoyltransferase 1

fabp :

Fatty acids binding protein

fas :

Fatty acid synthetase

fat/cd36 :

Fatty acid translocase

fatp :

Fatty acid transport protein

gpat :

Glycerol-3-phosphate acyltransferase

hsl :

Hormone sensitive lipase

pparα :

Peroxisome proliferator-activated receptor alpha

pparγ :

Peroxisome proliferator-activated receptor gamma

srebp-1 :

Sterol regulatory element-binding protein 1

References

  • AOAC (Association of Official Analytical Chemists) (2005) Official methods of analysis of the AOAC International, 18th Edition, AOAC International, Gaithersburg, MD, USA

  • Arnesen P, Krogdahl Å, Kristiansen IØ (1993) Lipogenic enzyme activities in liver of Atlantic salmon (Salmo salar, L). Comp Biochem Physiol B 105:541–546

    Article  Google Scholar 

  • Brusq JM, Ancellin N, Grondin P, Guillard R, Martin S, Saintillan Y, Issandou M (2006) Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res 47:1281–1288

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Zheng YM, Zhang MQ, Han Y, Zhang JP, Hu CQ (2020) Microarray expression profiling and raman spectroscopy reveal anti-fatty liver action of berberine in a diet-induced larval zebrafish model. Front Pharmacol 10:1504

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi YH (2016) Berberine hydrochloride protects C2C12 myoblast cells against oxidative stress-induced damage via induction of Nrf-2-mediated HO-1 expression. Drug Dev Res 77:310–318

    Article  CAS  PubMed  Google Scholar 

  • Davies SP, Hawley SA, Woods A, Carling D, Haystead TA, Hardie DG (1994) Purification of the AMP-activated protein kinase on ATP-γ-Sepharose and analysis of its subunit structure. FEBS J 223:351–357

    CAS  Google Scholar 

  • Day CP, James OFW (1998) Steatohepatitis: a tale of two “hits”? Gastroenterol 114:842–845

    Article  CAS  Google Scholar 

  • Doan HV, Hoseinifar SH, Jaturasitha S, Dawood MAO, Harikrishnan R (2020) The effects of berberine powder supplementation on growth performance, skin mucus immune response, serum immunity, and disease resistance of Nile tilapia (Oreochromis niloticus) fingerlings. Aquaculture 520:734927

    Article  CAS  Google Scholar 

  • Drape HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley M (1993) A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Radical Bio Med 15:353–363

    Article  Google Scholar 

  • Du ZY, Liu YJ, Tian LX, Wang JT, Wang Y, Liang GY (2005) Effect of dietary lipid level on growth, feed utilization and body composition by juvenile grass carp (Ctenopharyngodon idella). Aquacult Nutr 11:139–146

    Article  CAS  Google Scholar 

  • Du ZY, Clouet P, Huang LM, Degrace P, Zheng WH, He JG et al (2008) Utilization of different dietary lipid sources at high level in herbivorous grass carp (Ctenopharyngodon idella): mechanism related to hepatic fatty acid oxidation. Aquacult Nutr 14:77–92

    Article  CAS  Google Scholar 

  • Gaba S, Saini A, Singh G, Monga V (2021) An insight into the medicinal attributes of berberine derivatives: a review. Bioorg Med Chem 38:116143

    Article  CAS  PubMed  Google Scholar 

  • Gao W, Liu YJ, Tian LX, Mai KS, Liang GY, Yang HJ et al (2011) Protein-sparing capability of dietary lipid in herbivorous and omnivorous freshwater finfish: a comparative case study on grass carp (Ctenopharyngodon idella) and tilapia (Oreochromis niloticus × O. aureus). Aquacult Nutr 17:2–12

    Article  CAS  Google Scholar 

  • Garcia D, Shaw RJ (2017) AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell 66:789–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gavrilova O, Haluzik M, Matsusue K, Cutson JJ, Johnson L, Dietz KR et al (2003) Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem 278:34268–34276

    Article  CAS  PubMed  Google Scholar 

  • Goldberg IJ (1996) Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res 37:693–707

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Zhou Y, Zhao H, Chen W, Chen Y, Lin S (2019) Effect of dietary lipid level on growth, lipid metabolism and oxidative status of largemouth bass, Micropterus salmoides. Aquaculture 506:394–400

    Article  CAS  Google Scholar 

  • Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Bio 13:251–262

    Article  CAS  Google Scholar 

  • Ji C, Zhang DF, Li AH, Gong XN (2012) Effect of berberine hydrochloride on grass carp Ctenopharyngodon idella serum bactericidal activity against Edwardsiella ictaluri. Fish Shellfish Immunol 33:143–145

    Article  CAS  PubMed  Google Scholar 

  • Jia R, Cao LP, Du JL, He Q, Gu ZY, Jeney G et al (2020) Effects of high-fat diet on steatosis, endoplasmic reticulum stress and autophagy in liver of tilapia (Oreochromis niloticus). Front Mar Sci 7:363

    Article  Google Scholar 

  • Kerner J, Hoppel C (2000) Fatty acid import into mitochondria. Biochim BBA-Mol Cell Biol L 1486:1–17

    CAS  Google Scholar 

  • Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR et al (2009) Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol Endocrinol Metab 296:812–819

    Article  Google Scholar 

  • Kim SJ, Tang T, Abbott M, Viscarra JA, Wang Y, Sul HS (2016) AMPK phosphorylates desnutrin/ATGL and hormone-sensitive lipase to regulate lipolysis and fatty acid oxidation within adipose tissue. Mol Cell Biol 36:1961–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C et al (2004) Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 10:1344–1351

    Article  CAS  PubMed  Google Scholar 

  • Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS et al (2003) Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-α, iNOS, and IL-12 production in LPS-stimulated macrophages. Life Sci 73:1401–1412

    Article  CAS  PubMed  Google Scholar 

  • Li X, Jiang Y, Liu W, Ge X (2012) Protein-sparing effect of dietary lipid in practical diets for blunt snout bream (Megalobrama amblycephala) fingerlings: effects on digestive and metabolic responses. Fish Physiol Biochem 38:529–541

    Article  CAS  PubMed  Google Scholar 

  • Lindberg AV, Olivecrona G (2002) Lipoprotein lipase from rainbow trout differs in several aspects from the enzyme in mammals. Gene 292:213–223

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Huang K, Zheng Y, Gan W, Zuo T, Wang T (2020) Cloning of hepatic lipase and the effects of dietary nutrition on hepatic lipase expression in genetically improved farmed tilapia (Oreochromis niloticus). Fish Physiol Biochem 46:921–930

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-△△CT method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • López LM, Durazo E, Viana MT, Drawbridge M, Bureau DP (2009) Effect of dietary lipid levels on performance, body composition and fatty acid profile of juvenile white seabass, Atractoscion nobilis. Aquaculture 289:101–105

    Article  Google Scholar 

  • Lu KL, Xu WN, Wang LN, Zhang DD, Zhang CN, Liu WB (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

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu KL, Zhang DD, Wang LN, Xu WN, Liu WB (2016) Molecular characterization of carnitine palmitoyltransferase IA in Megalobrama amblycephala and effects on its expression of feeding status and dietary lipid and berberine. Comp Biochem Physiol B Biochem Mol Biol 191:20–25

    Article  CAS  PubMed  Google Scholar 

  • Lu KL, Wang LN, Zhang DD, Liu WB, Xu WN (2017) Berberine attenuates oxidative stress and hepatocytes apoptosis via protecting mitochondria in blunt snout bream Megalobrama amblycephala fed high-fat diets. Fish Physiol Biochem 43:65–76

    Article  CAS  PubMed  Google Scholar 

  • Ma J, Shao Q, Xu Z, Zhou F (2013) Effect of dietary n-3 highly unsaturated fatty acids on growth, body composition and fatty acid profiles of juvenile black seabream, Acanthopagrus schlegeli (Bleeker). J World Aquacult Soc 44:311–325

    Article  CAS  Google Scholar 

  • Matsumoto T, Terai S, Oishi T, Kuwashiro S, Fujisawa K, Yamamoto N et al (2010) Medaka as a model for human nonalcoholic steatohepatitis. Dis Model Mech 3:431–440

    Article  CAS  PubMed  Google Scholar 

  • Ming JH, Ye JY, Zhang YX, Xu P, Xie J (2015) Effects of dietary reduced glutathione on growth performance, non-specific immunity, antioxidant capacity and expression levels of IGF-I and HSP70 mRNA of grass carp (Ctenopharyngodon idella). Aquaculture 438:39–46

    Article  CAS  Google Scholar 

  • Ming JH, Ye JY, Zhang YX, Xu QY, Yang X, Shao XP, Qiang J, Xu P (2020) Optimal dietary curcumin improved growth performance, and modulated innate immunity, antioxidant capacity and related genes expression of NF-κB and Nrf2 signaling pathways in grass carp (Ctenopharyngodon idella) after infection with Aeromonas hydrophila. Fish Shellfish Immunol 97:540–553

    Article  CAS  PubMed  Google Scholar 

  • Minghetti M, Leaver MJ, Tocher DR (2011) Transcriptional control mechanisms of genes of lipid and fatty acid metabolism in the Atlantic salmon (Salmo salar L.) established cell line, SHK-1. BBA-Mol Cell Biol L 1811:194–202

    CAS  Google Scholar 

  • Ministry of Agriculture and Rural Affairs of China (2021) China fisheries statistical yearbook in 2021. China Agricultural Press, Beijing, p 25

    Google Scholar 

  • Morais S, Knoll-Gellida A, André M, Barthe C, Babin PJ (2007) Conserved expression of alternative splicing variants of peroxisomal acyl-CoA oxidase 1 in vertebrates and developmental and nutritional regulation in fish. Physiol Genomics 28:239–252

    Article  CAS  PubMed  Google Scholar 

  • Nie MM, Lu YL, Zou CC, Wang LJ, Zhang PJ, You F (2020) Insight into AMPK regulation mechanism in vivo and in vitro: responses to low temperatures in the olive flounder Paralichthys olivaceus. J Therm Biol 91:102640

    Article  CAS  PubMed  Google Scholar 

  • Oku H, Umino T (2008) Molecular characterization of peroxisome proliferator-activated receptors (PPARs) and their gene expression in the differentiating adipocytes of red sea bream Pagrus major. Comp Biochem Physiol B Biochem Mol Biol 151:268–277

    Article  PubMed  Google Scholar 

  • Park H, Kaushik VK, Constant S, Prentki M, Przybytkowski E, Ruderman NB, Saha AK (2002) Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Bio Chem 277:32571–32577

    Article  CAS  Google Scholar 

  • Ran C, Xie M, Li J, Xie Y, Ding Q, Li Y et al (2021) Dietary nucleotides alleviate hepatic lipid deposition via exogenous AMP-mediated AMPK activation in zebrafish. J Nutr 151:2986–2996

    Article  PubMed  Google Scholar 

  • Regost C, Arzel J, Cardinal M, Robin J, Laroche M, Kaushik SJ (2001) Dietary lipid level, hepatic lipogenesis and flesh quality in turbot (Psetta maxima). Aquaculture 193:291–309

    Article  CAS  Google Scholar 

  • Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63

    Article  CAS  PubMed  Google Scholar 

  • Ren G, Guo JH, Qian YZ, Kong WJ, Jiang JD (2020) Berberine improves glucose and lipid metabolism in HepG2 cells through AMPKα1 activation. Front Pharmacol 11:647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shan WJ, Huang L, Zhou Q, Meng FC, Li XS (2011) Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multi-functional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Eur J Med Chem 46:5885–5893

    Article  CAS  PubMed  Google Scholar 

  • Tang T, Hu Y, Peng M, Chu W, Hu Y, Zhong L (2019) Effects of high-fat diet on growth performance, lipid accumulation and lipid metabolism-related MicroRNA/gene expression in the liver of grass carp (Ctenopharyngodon idella). Comp Biochem Phys B 234:34–40

    Article  CAS  Google Scholar 

  • Tessari P, Coracina A, Cosma A, Tiengo A (2009) Hepatic lipid metabolism and non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 19:291–302

    Article  CAS  PubMed  Google Scholar 

  • Vardi N, Parlakpinar H, Ozturk F, Ates B, Gul M, Cetin A et al (2008) Potent protective effect of apricot and beta-carotene on methotrexate-induced intestinal oxidative damage in rats. Food Chem Toxicol 46:3015–3022

    Article  CAS  PubMed  Google Scholar 

  • Viollet B, Andreelli F, Jørgensen SB, Perrin C, Flamez D, Mu J et al (2003) Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. Biochem Soc Trans 31:216–219

    Article  CAS  PubMed  Google Scholar 

  • Wakil SJ, Abu-Elheiga LA (2009) Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 50:138–143

    Article  Google Scholar 

  • Wang Y, Zidichouski JA (2018) Update on the benefits and mechanisms of action of the bioactive vegetal alkaloid berberine on lipid metabolism and homeostasis. Cholesterol 2018:7173920

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang JT, Liu YJ, Tian LX, Mai KS, Du ZY, Wang Y, Yang HJ (2005) Effect of dietary lipid level on growth performance, lipid deposition, hepatic lipogenesis in juvenile cobia (Rachycentron canadum). Aquaculture 249:439–447

    Article  CAS  Google Scholar 

  • Wang L, Zhang W, Gladstone S, Ng WK, Zhang J, Shao Q (2019) Effects of isoenergetic diets with varying protein and lipid levels on the growth, feed utilization, metabolic enzymes activities, antioxidative status and serum biochemical parameters of black sea bream (Acanthopagrus schlegelii). Aquaculture 513:734397

    Article  CAS  Google Scholar 

  • Wang L, Xu B, Sagada G, Ng WK, Chen K, Zhang J, Shao Q (2021) Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets. Br J Nutr 125:481–493

    Article  CAS  PubMed  Google Scholar 

  • Xu WN, Chen DH, Chen QQ, Liu WB (2017) Growth performance, innate immune responses and disease resistance of fingerling blunt snout bream, Megalobrama amblycephala adapted to different berberine-dietary feeding modes. Fish Shellfish Immunol 68:458–465

    Article  CAS  PubMed  Google Scholar 

  • Yan J, Liao K, Wang T, Mai K, Xu W, Ai Q (2015) Dietary lipid levels influence lipid deposition in the liver of large yellow croaker (Larimichthys crocea) by regulating lipoprotein receptors, fatty acid uptake and triacylglycerol synthesis and catabolism at the transcriptional level. PLoS One 10:e0129937

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoon M (2009) The role of PPARα in lipid metabolism and obesity: focusing on the effects of estrogen on PPARα actions. Pharmacol Res 60:151–159

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Li C, Wang L, Ji H, Zhu T (2015) Hepatoprotective effects of a Chinese herbal formulation, Yingchen decoction, on olaquindox-induced hepatopancreas injury in Jian carp (Cyprinus carpio var. Jian). Fish Physiol Biochem 41:153–163

    Article  PubMed  Google Scholar 

  • Zhou W, Rahimnejad S, Lu K, Wang L, Liu W (2019) Effects of berberine on growth, liver histology, and expression of lipid-related genes in blunt snout bream (Megalobrama amblycephala) fed high-fat diets. Fish Physiol Biochem 45:83–91

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Bian H, Wang L, Sun X, Xu X, Yan H et al (2019) Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radical Bio Med 141:192–204

    Article  CAS  Google Scholar 

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Funding

This work was jointly supported by the Basic and Public Welfare Research Project of Zhejiang Province in China (LGN20C190006), Research on Public Welfare Technology Application of Science and Technology Project of Huzhou in China (2020GZ09), Earmarked Fund for China Agriculture Research System (CARS-45) and National Natural Science Foundation of China (31372544).

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Jianhua Ming: Methodology, Conceptualization, Investigation, Data curation, Formal analysis, Writing-original draft, review and editing, Supervision, Funding acquisition. Ting Wang and Tinghui Wang: Investigation, Data curation. Jinyun Ye: Conceptualization, Writing-review & editing, Supervision, Funding acquisition. Yixiang Zhang: Methodology, Validation. Xia Yang: Methodology, Formal analysis. Xianping Shao: Methodology, Data curation. Zhongying Ding: Methodology, Visualization.

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Correspondence to Jian-Hua Ming.

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All of the experimental procedures involving fish were performed in accordance with relevant national guidelines and approved by the Institutional Animal Care and Use Committee of Huzhou University, China.

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Ming, JH., Wang, T., Wang, TH. et al. Effects of dietary berberine on growth performance, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus) fed high-fat diets. Fish Physiol Biochem 49, 769–786 (2023). https://doi.org/10.1007/s10695-022-01143-8

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