Skip to main content
SpringerLink
Log in

Systemic effect of dietary lipid levels and α-lipoic acid supplementation on nutritional metabolism in zebrafish (Danio rerio): focusing on the transcriptional level

  • Published:
Fish Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Considering the excessive lipid accumulation status caused by the increased dietary lipid intake in farmed fish, this study aimed to investigate the systemic effect of dietary lipid levels and α-lipoic acid supplementation on nutritional metabolism in zebrafish. A total of 540 male zebrafish (0.17 g) were fed with normal (CT) and high lipid level (HL) diets for 6 weeks, then fed on 1000 mg/kg α-lipoic acid supplementation diets for the second 6 weeks. HL diets did not affect whole fish protein content, but increased ASNS expression (P < 0.05). Dietary α-lipoic acid increased whole fish protein content, and decreased the expressions of protein catabolism-related genes in muscle of high lipid level groups (P < 0.05). Furthermore, HL diets increased the whole fish lipid content and the expressions of gluconeogenesis and lipogenesis-related genes (P < 0.05), and α-lipoic acid counteracted these effects and decreased the whole fish triglyceride and cholesterol contents and expressions of lipogenesis-related genes, with the enhanced expressions of lipolytic genes, especially in high lipid groups (P < 0.05). HL diets did not affect hepatocyte mitochondrial quantity or the mRNA expressions of mitochondrial biogenesis and electron transport chain-related genes; they were significantly increased by dietary α-lipoic acid (P < 0.05). These results indicated that high dietary lipid promotes lipid accumulation, while α-lipoic acid increases protein content in association of enhanced lipid catabolism. Thus, dietary α-lipoic acid supplementation could reduce lipid accumulation under high lipid, which provides a promising new approach in solving the problem of lipid accumulation in farmed fish.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ACC:

acetyl-CoA carboxylase

AMPK:

AMP-activated protein kinase

APN:

aminopeptidase n

ASNS:

asparagine synthetase

ATGL:

adipose triglyceride lipase

ATP5α1:

ATP synthase mitochondrial F1 complex alpha subunit.

COX5ab:

cytochrome c oxidase subunit Vab

CPT1:

carnitine palmitoyltransferase 1

CT:

control

DGAT2:

diacylglycerol acyltransferase 2

FAS:

fatty acid synthase

GDH1a:

glutamate dehydrogenase 1a

GDH1b:

glutamate dehydrogenase 1b

GK:

glucokinase

G6Pase:

glucose-6-phosphatase

HL:

high lipid

HSL:

hormone-sensitive lipase

LPL:

lipoprotein lipase

mTOR:

mechanistic target of rapamycin

NRF1:

nuclear respiratory factor 1

PEPCK:

phosphoenolpyruvate carboxykinase

PEPT1:

peptide transporter 1

PFK:

Phosphofructokinase

PGC-1α:

peroxisome proliferator-activated receptor gamma, coactivator 1 alpha

PK:

pyruvate kinase

SGLT-1:

sodium-dependent glucose co-transporter 1

SIRT1:

sirtuin 1

TFAM:

mitochondrial transcription factor A

TEM:

transmission electron microscopy

UQCRC2:

ubiquinol–cytochrome c reductase core protein II.

References

  • Borges P, Valente LM, Véron V, Dias K, Panserat S, Médale F (2014) High dietary lipid level is associated with persistent hyperglycaemia and downregulation of muscle Akt-mTOR pathway in senegalese sole (Solea senegalensis). PLoS One 9(7):e102196

    PubMed  PubMed Central  Google Scholar 

  • Boujard T, Gélineau A, Covès D, Corrazea G, Duttob G, Gassetb E, Kaushika S (2004) Regulation of feed intake, growth, nutrient and energy utilisation in European sea bass (Dicentrarchus labrax) fed high fat diets. Aquaculture 231(1–4):529–545

    Google Scholar 

  • Brandão LV, Pereira Filho M, Guimarães SF, Fonseca FA (2009) Reduction of protein levels and methionine and/or lysine supplementation in diets and their effects in total ammonia nitrogen excretion of tambaqui juveniles (Colossoma macropomum Cuvier, 1818). Acta Amazon 39(3):675–680

    Google Scholar 

  • Butler JA, Hagen TM, Moreau R (2009) Lipoic acid improves hypertriglyceddemia by stimulating triacylg1ycerol clearance and down regulating liver triacylgIycerol secretion. Arch Biochem Biophys 485(1):63–71

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng Z, Li J, Zhang B, Fang Z, Sun J, Bai D, Sun J, Qiao X (2017) Verification of protein sparing by feeding carbohydrate to common carp Cyprinus carpio. Chin J Oceanol Limnol 35(2):251–257

    CAS  Google Scholar 

  • Fernández-Galilea M, Pérez-Matute P, Prieto-Hontoria PL, Houssierde M, Burrellf MA, Langin D, Martíneza JA, Moreno-Aliaga MJ (2015) α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects. Biochim Biophys Acta 1851(3):273–281

    PubMed  Google Scholar 

  • Figueiredo-Silva AC, Corraze G, Borges P, Valente LMP (2010) Dietary protein/lipid level and protein source effects on growth, tissue composition and lipid metabolism of blackspot seabream (Pagellus bogaraveo). Aquac Nutr 16(2):173–187

    CAS  Google Scholar 

  • Gao J, Zhu ZR, Ding HQ, Qian ZM, Zhu L, Ke Y (2007) Vulnerability of neurons with mitochondrial dysfunction to oxidative stress is associated with down-regulation of thioredoxin. Neurochem Int 50(2):379–385

    CAS  PubMed  Google Scholar 

  • Gao W, Liu YJ, Tian LX, Mai KS, Liang GY, Yang HJ, Huai MY, Luo WJ (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). Aquac Nutr 17(1):2–12

  • Gupte AA, Bomhoff GL, Morris JK, Gorres BK, Geiger PC (2009) Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats. J Appl Physiol 106(4):1425–1434

    CAS  PubMed  Google Scholar 

  • Hamano Y (2002) Influence of lipoic acid on lipid metabolism and β-adrenergic response to intravenous or oral administration of clenbuterol in broiler chickens. Reprod Nutr Dev 42(4):307–316

    CAS  PubMed  Google Scholar 

  • Hamano Y (2006) Effects of dietary lipoic acid on plasma lipid, in vivo insulin sensitivity, metabolic response to corticosterone and in vitro lipolysis in broiler chickens. Br J Nutr 95(6):1094–1101

    CAS  PubMed  Google Scholar 

  • Handy RD, Poxton MG (1993) Nitrogen pollution in mariculture: toxicity and excretion of nitrogenous compounds by marine fish. Rev Fish Biol Fish 3(3):205–241

    Google Scholar 

  • He AY, Ning LJ, Chen LQ, Chen YL, Xing Q, Li JM, Qiao F, Li AL, Zhang ML, Du ZY (2015) Systemic adaptation of lipid metabolism in response to low- and high-fat diet in Nile tilapia (Oreochromis niloticus). Physiol Rep 3(8):e12485

  • Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ (1997) Stimulation by α-lipoic acid of glucose transport activity in skeletal muscle of lean and obese zucker rats. Life Sci 61(8):805–812

    CAS  PubMed  Google Scholar 

  • Huerta AE, Prieto-Hontoria PL, Sáinz N, Martinez JA, Moreno-Aliaga MJ (2016) Supplementation with α-lipoic acid alone or in combination with eicosapentaenoic acid modulates the inflammatory status of healthy overweight or obese women consuming an energy-restricted diet. J Nutr 146(4):115.224105

    Google Scholar 

  • Huong DT, Ide T (2008) Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. Br J Nutr 100(1):79–87

    CAS  PubMed  Google Scholar 

  • Jia R, Bao YH, Zhang Y, Ji C, Zhao LH, Zhang JY, Gao CQ, Ma QG (2014) Effects of dietary α-lipoic acid, acetyl-l-carnitine, and sex on antioxidative ability, energy, and lipid metabolism in broilers. Poult Sci 93(11):2809–2817

    CAS  PubMed  Google Scholar 

  • Jobling M (2012) National research council (NRC): nutrient requirements of fish and shrimp. Aquac Int 20(3):601–602

    Google Scholar 

  • Kagan VE, Shvedova A, Serbinova E, Kagan S, Swanson C, Powell R, Packer L (1992) Dihydrilipoic acid: a universal antioxidant both in the membrane and in the aqueous phase. Biochem Pharmacol 44:1637–1649

    CAS  PubMed  Google Scholar 

  • Karga J, Mandal SC (2016) Effect of different feeds on the growth, survival and reproductive performance of zebrafish, Danio rerio, (Hamilton, 1822). Aquac Nutr 23(2):406–413

    Google Scholar 

  • Kirchner S, Seixas P, Kaushik S, Panserat S (2005) Effects of low protein intake on extra-hepatic gluconeogenic enzyme expression and peripheral glucose phosphorylation in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol B Biochem Mol Biol 140(2):333–340

    CAS  PubMed  Google Scholar 

  • Kütter MT, Monserrat JM, Primel EG, Caldas SS, Tesser MB (2012) Effects of dietary α-lipoic acid on growth, body composition and antioxidant status in the Plata pompano Trachinotus marginatus, (Pisces, Carangidae). Aquaculture 368-369:29–35

    Google Scholar 

  • Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, Kim MS, Kim SW, Lee KU, Park JY (2005) Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 332(3):885–891

    CAS  PubMed  Google Scholar 

  • Li SL, Mai KS, Xu W, Yuan YY, Zhang YJ, Zhou HH, Ai QH (2016a) Effects of dietary lipid level on growth, fatty acid composition, digestive enzymes and expression of some lipid metabolism related genes of orange-spotted grouper larvae (Epinephelus coioides H.). Aquac Res 47(8):2481–2495

    CAS  Google Scholar 

  • Li AY, Yuan XC, Liang XF, Liu LW, Li J, Li B, Fang JG, Li J, He S, Xue M, Wang J, Tao YX (2016b) Adaptations of lipid metabolism and food intake in response to low and high fat diets in juvenile grass carp (ctenopharyngodon idellus). Aquaculture 457:43–49

    CAS  Google Scholar 

  • Li JM, Li LY, Qin X, Ning LJ, Lu DL, Li DL, Zhang ML, Wang X, Du ZY (2017) Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio. Sci Rep 7:40815

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liao ML, Ren TJ, Chen W, Han YZ, Liu CM, Jiang ZQ, Wang FQ (2015) Effects of dietary lipid level on growth performance, body composition and digestive enzymes activity of juvenile sea cucumber, Apostichopus japonicus. Aquac Res 48(1):92–101

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25(4):402–408

    CAS  Google Scholar 

  • Long J, Wang X, Gao H, Liu Z, Liu CS, Miao MY, Cui X, Packer L, Liu JK (2007) D-Galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid. Biogerontology 8(3):373–381

    CAS  PubMed  Google Scholar 

  • Meng Y, Li C, Qin Q, Tong Y, Zhu R, Xu G, Shi Y, Ghi J, Ma R (2017) Dietary lipid levels affect the growth performance, lipid deposition, and antioxidative capacity of juvenile scaleless carp. J World Aquacult Soc 49(4):788–797

  • Miles RD, Chapman FA (2008) The concept of ideal protein in formulation of aquaculture feeds. University of florida IFAS Extension FA 144

  • Moon TW (1995) Tissue carbohydrate metabolism, gluconeogenesis, and hormonal and environmental influences. Biochem Mol Biol Fish 4(06):65–100

    CAS  Google Scholar 

  • Morais S, Bell JG, Robertson DA, Roy WJ, Morris PC (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(1):101–119

    CAS  Google Scholar 

  • O’Brine TM, Vrtělová J, Snellgrove DL, Davies SJ, Sloman KA (2015) Growth, oxygen consumption, and behavioral responses of Danio rerio to variation in dietary protein and lipid levels. Zebrafish 12:296–304

    PubMed  Google Scholar 

  • Orire AM, Sadiku S (2011) Protein sparing effects of lipids in the practical diets of oreochromis niloticus (Nile tilapia). Niger J Basic Appl Sci 19(1):556–558

    Google Scholar 

  • Rodriguez MC, Macdonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsky MA (2010) Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve 35(2):235–242

    Google Scholar 

  • Santos RA, Caldas S, Primel EG, Tesser MB, Monserrat JM (2016) Effects of lipoic acid on growth and biochemical responses of common carp fed with carbohydrate diets. Fish Physiol Biochem 42(6):1–9

    Google Scholar 

  • Schmidt RE, Feng D, Wang Q, Green KG, Snipes LL, Yamin M, Brines M (2011) Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2Akita) diabetic mouse sympathetic ganglia. Exp Neurol 232(2):126–135

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 1790(10):1149–1160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shen W, Liu K, Tian C (2008) R -α-Lipoic acid and acetyl- l -carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes. Diabetologia 51(1):165–174

    CAS  PubMed  Google Scholar 

  • Shen W, Hao J, Feng Z, Tian C, Chen W, Packer L, Shi X, Zang W, Liu J (2011) Lipoamide or lipoic acid stimulates mitochondrial biogenesis in 3T3-L1 adipocytes via the endothelial NO synthase-cGMP-protein kinase G signalling pathway. Br J Pharmacol 162:1213–1224

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi XC, Jin A, Sun J, Yang Z, Tian JJ, Ji H, Yu HB, Li Y, Zhou JS, Du ZY, Chen LQ (2017) α-Lipoic acid ameliorates n-3 highly-unsaturated fatty acids induced lipid peroxidation via regulating antioxidant defenses in grass carp (Ctenopharyngodon idellus). Fish Shellfish Immunol 67:359–367

    CAS  PubMed  Google Scholar 

  • Shi XC, Jin A, Sun J, Tian JJ, Ji H, Chen LQ, Du ZY (2018) The protein-sparing effect of α-lipoic acid in juvenile grass carp, Ctenopharyngodon idellus: effects on lipolysis, fatty acid β-oxidation, and protein synthesis. Br J Nutr:1–11

  • Streeper RS, Henriksen EJ, Jacob S (1997) Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Phys 273(1):185–191

    Google Scholar 

  • Timmers S, Bosch JDVD, Towler MC, Schaart G, Moonen-Kornips E, Mensink RP, Hesselink MK, Hardie DG, Schrauwen P (2010) Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation. J Lipid Res 51(2):352–359

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tocher DR (2003) Metabolism and functions of lipids and fatty acids in teleost fish. Rev Fish Sci 11(2):78

    Google Scholar 

  • Tranulis MA, Christophersen B, Blom AK, Borrebaek B (1991) Glucose dehydrogenase, glucose-6-phosphate dehydrogenase and hexokinase in liver of rainbow trout (Salmo gairdneri). Effects of starvation and temperature variations. Comp Biochem Physiol B 99(3):687–691

    CAS  PubMed  Google Scholar 

  • Trattner S, Pickova J, Park KH, Rinchard J, Dabrowski K (2007) Effects of α-lipoic and ascorbic acid on the muscle and brain fatty acids and antioxidant profile of the South American pacu Piaractus mesopotamicus. Aquaculture 273(1):158–164

    CAS  Google Scholar 

  • Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA (2012) Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity 20(10):1974–1983

    CAS  PubMed  Google Scholar 

  • Wang Y, Li XJ, Guo YM, Chan L, Guan X (2010) α-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate–activated protein kinase–peroxisome proliferator-activated receptor-γ coactivator-1α signaling in the skeletal muscle of aged mice. Metab Clin Exp 59(7):967–976

    CAS  PubMed  Google Scholar 

  • Williams KC, Barlow CG, Rodgers L, Hockings I, Agcopra C, Ruscoe I (2003) Asian seabass Lates calcarifer perform well when fed pelleted diets high in protein and lipid. Aquaculture 225(1):191–206

    Google Scholar 

  • Wu BL, Xiong XQ, Xie SQ, Wang JW (2016) Dietary lipid and gross energy affect protein utilization in the rare minnow Gobiocypris rarus. Chin J Ocean Limnol 34(4):740–748

    CAS  Google Scholar 

  • Yang RL, Li W, Shi YH, Le GW (2008) Lipoic acid prevents high-fat diet-induced dyslipidemia and oxidative stress: a microarray analysis. Nutrition 24(6):582–588

    PubMed  Google Scholar 

  • Yang HT, Zou SS, Zhai LJ, Wang Y, Zhang FM, An LG, Yang GW (2017) Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine. Fish Shellfish Immunol 71:S1050464817305946

    Google Scholar 

  • Yuan YH, Li SL, Zhang L, Mai KS, Xu W, Ai QH (2017) Influence of dietary lipid on growth performance and some lipogenesis-related gene expression of tongue sole (Cynoglossus semilaevis) larvae. Aquac Res 48(3):n/a-n/a

Download references

Acknowledgments

Thanks are due to Jingjing Tian, Xiaochen Shi, and Bin-xin Zhang for their assistance in the study.

Funding

This work was financially supported by the project of Shaanxi Science and Technology innovation project plan (2015KTTSNY01-05), the Innovative Talent Promotion Program (2018TD-021), and the project of Shaanxi Science Key R & D plan (2018NY-024).

Author information

Authors and Affiliations

  1. College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China

    Chen-cui Huang, Jian Sun, Hong Ji, Xing-da Xie, Zhi-guang Chang & Wei Deng

  2. School of Arts and Sciences, University of Houston-Victoria, 3007, North Ben Wilson, Victoria, TX, 77901, USA

    Gen Kaneko

Authors
  1. Chen-cui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gen Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xing-da Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi-guang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors conceived and designed this experiment. Chen-cui Huang and Xing-da Xie performed the experiment and contributed to the analysis of data. Chen-cui Huang, Jian Sun, Hong Ji, Gen Kaneko, Xing-da Xie, Zhi-guang Chang, and Wei Deng co-wrote the manuscript. All authors read and approved this manuscript.

Corresponding author

Correspondence to Hong Ji.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 1943 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Cc., Sun, J., Ji, H. et al. Systemic effect of dietary lipid levels and α-lipoic acid supplementation on nutritional metabolism in zebrafish (Danio rerio): focusing on the transcriptional level. Fish Physiol Biochem 46, 1631–1644 (2020). https://doi.org/10.1007/s10695-020-00795-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10695-020-00795-8

Keywords

Search

Navigation