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Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFα

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Abstract

Purpose

The beneficial effects of a seafood-rich diet are highly documented and can be attributed to both n-3 polyunsaturated fatty acids and other less studied nutritional components including protein and antioxidants. The aim of the work was to investigate whether an under-utilized seafood source, eggs (roe) and sperm (milt) from herring (Clupea harengus), can affect lipid metabolism and inflammation in a mouse model transgenic for human tumor necrosis factor alpha (hTNFα).

Methods

A high-fat control diet (25% total fats, 20% protein, w/w) or high-fat diets supplemented with herring roe (3.7% fat, 15% protein, w/w), or milt (1.3% fat, 15% protein) were administered to female C57BL/6 hTNFα mice. After 2 weeks, hepatic enzyme activity, gene expression, lipid and fatty acid composition, fatty acid composition of epididymal adipose tissue, and plasma lipid and cytokine levels were determined.

Results

Animals fed herring roe and milt displayed an increased hepatic fatty acid β-oxidation and reduced fatty acid synthase activity. However, while plasma TAG was reduced, hepatic TAG and plasma and hepatic cholesterol levels were increased by the herring diets. Both herring diets led to a substantial shift in the n-6:n-3 ratio in both liver and ovarian white adipose tissue. The herring diets also increased plasma carnitine and reduced the carnitine precursor trimethyllysine. Plasma short-chained acylcarnitine esters were significantly increased, which may reflect an increased β-oxidation of long-chained fatty acids. In addition, the diets tended to reduce the plasma levels of pro-inflammatory cytokines.

Conclusion

Herring roe or milt diets enhanced lipid catabolism and influenced the chronic inflammatory state in hTNFα-transgenic mice.

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Abbreviations

AADAC:

Arylacetamide deacetylase

ACACA:

Acetyl-CoA carboxylase alpha

ACOX1:

Acyl-CoA oxidase 1

ACS:

Acyl-CoA synthetase

CPT:

Carnitine palmitoyltransferase

CSF2:

Colony-stimulating factor 2 (granulocyte-macrophage)

CYP7A1:

Cytochrome P450, family 7, subfamily A, polypeptide 1

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

FADS:

Fatty acid desaturase

FASN:

Fatty acid synthase

HMGCS:

3-hydroxy-3-methylglutaryl-coenzyme a synthase

hTNFα:

Human tumor necrosis factor alpha

LDLR:

Low-density lipoprotein receptor

PPAR:

Peroxisome proliferator-activated receptor

SCD1:

Stearoyl-CoA desaturase 1

WAT:

White adipose tissue

References

  1. Muoio DM, Newgard CB (2006) Obesity-related derangements in metabolic regulation. Annu Rev Biochem 75:367–401

    Article  CAS  Google Scholar 

  2. Monteiro R, Azevedo I (2010) Chronic inflammation in obesity and the metabolic syndrome. Mediat Inflamm 36(2):319–326

    Google Scholar 

  3. Tilg H, Moschen AR (2008) Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 14(3–4):222–231

    CAS  Google Scholar 

  4. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95(5):2409–2415

    Article  CAS  Google Scholar 

  5. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91

    Article  CAS  Google Scholar 

  6. Glosli H, Gudbrandsen OA, Mullen AJ, Halvorsen B, Rost TH, Wergedahl H, Prydz H, Aukrust P, Berge RK (2005) Down-regulated expression of PPAR alpha target genes, reduced fatty acid oxidation and altered fatty acid composition in the liver of mice transgenic for hTNFalpha. Biochim Biophys Acta 1734(3):235–246

    Article  CAS  Google Scholar 

  7. Flachs P, Rossmeisl M, Bryhn M, Kopecky J (2009) Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clin Sci (Lond) 116(1):1–16

    Article  CAS  Google Scholar 

  8. Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI (2007) n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes 56(4):1034–1041

    Article  CAS  Google Scholar 

  9. Calder PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83(6 Suppl):1505S–1519S

    CAS  Google Scholar 

  10. Kato M, Ogawa H, Kishida T, Ebihara K (2011) Hypocholesterolaemic effect of water-insoluble fish protein from Alaska pollock in ovariectomised rats is not abolished by methionine addition. Br J Nutr 106(1):57–62

    Article  CAS  Google Scholar 

  11. Shukla A, Bettzieche A, Hirche F, Brandsch C, Stangl GI, Eder K (2006) Dietary fish protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model. Br J Nutr 96(4):674–682

    CAS  Google Scholar 

  12. Wergedahl H, Gudbrandsen OA, Rost TH, Berge RK (2009) Combination of fish oil and fish protein hydrolysate reduces the plasma cholesterol level with a concurrent increase in hepatic cholesterol level in high-fat-fed wistar rats. Nutrition 25(1):98–104

    Article  CAS  Google Scholar 

  13. Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mork S, Berge RK (2004) Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA: cholesterol acyltransferase activity in liver of zucker rats. J Nutr 134(6):1320–1327

    CAS  Google Scholar 

  14. Fitzgerald AJ, Rai PS, Marchbank T, Taylor GW, Ghosh S, Ritz BW, Playford RJ (2005) Reparative properties of a commercial fish protein hydrolysate preparation. Gut 54(6):775–781

    Article  CAS  Google Scholar 

  15. Duarte J, Vinderola G, Ritz B, Perdigon G, Matar C (2006) Immunomodulating capacity of commercial fish protein hydrolysate for diet supplementation. Immunobiology 211(5):341–350

    Article  CAS  Google Scholar 

  16. Huynh MD, Kitts DD, Hu C, Trites AW (2007) Comparison of fatty acid profiles of spawning and non-spawning Pacific herring, Clupea harengus pallasi. Comp Biochem Physiol B Biochem Mol Biol 146(4):504–511

    Article  Google Scholar 

  17. Tocher DR, Sargent JR (1984) Analyses of lipids and fatty acids in ripe roes of some northwest European marine fish. Lipids 19(7):492–499

    Article  CAS  Google Scholar 

  18. Falch E, Storseth TR, Aursand M (2006) Multi-component analysis of marine lipids in fish gonads with emphasis on phospholipids using high resolution NMR spectroscopy. Chem Phys Lipids 144(1):4–16

    Article  CAS  Google Scholar 

  19. Moriya H, Hosokawa M, Miyashita K (2007) Combination effect of herring roe lipids and proteins on plasma lipids and abdominal fat weight of mouse. J Food Sci 72(5):C231–C234

    Article  CAS  Google Scholar 

  20. Higuchi T, Shirai N, Suzuki H (2006) Effects of dietary herring roe lipids on plasma lipid, glucose, insulin, and adiponectin concentrations in mice. J Agric Food Chem 54(10):3750–3755

    Article  CAS  Google Scholar 

  21. Hayward MD, Jones BK, Saparov A, Hain HS, Trillat AC, Bunzel MM, Corona A, Li-Wang B, Strenkowski B, Giordano C, Shen H, Arcamone E, Weidlick J, Vilensky M, Tugusheva M, Felkner RH, Campbell W, Rao Y, Grass DS, Buiakova O (2007) An extensive phenotypic characterization of the hTNFalpha transgenic mice. BMC Physiol 7:13

    Article  Google Scholar 

  22. Xiao L, Mjøs SA, Haugsgjerd BO Efficiencies of three common lipid extraction methods evaluated by calculating mass balances of the fatty acids. J Food Compo Anal, (in press)

  23. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917

    Article  CAS  Google Scholar 

  24. Vernez L, Wenk M, Krahenbuhl S (2004) Determination of carnitine and acylcarnitines in plasma by high-performance liquid chromatography/electrospray ionization ion trap tandem mass spectrometry. Rapid Commun Mass Spectrom 18(11):1233–1238

    Article  CAS  Google Scholar 

  25. Berge RK, Flatmark T, Osmundsen H (1984) Enhancement of long-chain acyl-CoA hydrolase activity in peroxisomes and mitochondria of rat liver by peroxisomal proliferators. Eur J Biochem 141(3):637–644

    Article  CAS  Google Scholar 

  26. Madsen L, Rustan AC, Vaagenes H, Berge K, Dyroy E, Berge RK (1999) Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference. Lipids 34(9):951–963

    Article  CAS  Google Scholar 

  27. Madsen L, Froyland L, Dyroy E, Helland K, Berge RK (1998) Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J Lipid Res 39(3):583–593

    CAS  Google Scholar 

  28. Skorve J, Al-Shurbaji A, Asiedu D, Bjorkhem I, Berglund L, Berge RK (1993) On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. J Lipid Res 34(7):1177–1185

    CAS  Google Scholar 

  29. Mahe G, Ronziere T, Laviolle B, Golfier V, Cochery T, De Bray JM, Paillard F (2010) An unfavorable dietary pattern is associated with symptomatic ischemic stroke and carotid atherosclerosis. J Vasc Surg 52(1):62–68

    Article  Google Scholar 

  30. Fessler MB, Rudel LL, Brown JM (2009) Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol 20(5):379–385

    Article  CAS  Google Scholar 

  31. Beier K, Volkl A, Fahimi HD (1997) TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal proteins in rat liver. FEBS Lett 412(2):385–387

    Article  CAS  Google Scholar 

  32. Hsu MH, Savas U, Griffin KJ, Johnson EF (2001) Identification of peroxisome proliferator-responsive human genes by elevated expression of the peroxisome proliferator-activated receptor alpha in HepG2 cells. J Biol Chem 276(30):27950–27958

    Article  CAS  Google Scholar 

  33. Lo V, Erickson B, Thomason-Hughes M, Ko KW, Dolinsky VW, Nelson R, Lehner R (2010) Arylacetamide deacetylase attenuates fatty-acid-induced triacylglycerol accumulation in rat hepatoma cells. J Lipid Res 51(2):368–377

    Article  CAS  Google Scholar 

  34. Nookaew I, Gabrielsson BG, Holmang A, Sandberg AS, Nielsen J (2010) Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice. PLoS One 5(8):e12361

    Article  Google Scholar 

  35. Burri L, Bjorndal B, Wergedahl H, Berge K, Bohov P, Svardal A, Berge RK (2011) Tetradecylthioacetic acid increases hepatic mitochondrial beta-oxidation and alters fatty acid composition in a mouse model of chronic inflammation. Lipids 46(8):679–689

    Article  CAS  Google Scholar 

  36. Hosomi R, Fukunaga K, Arai H, Nishiyama T, Yoshida M (2009) Effects of dietary fish protein on serum and liver lipid concentrations in rats and the expression of hepatic genes involved in lipid metabolism. J Agric Food Chem 57(19):9256–9262

    Article  CAS  Google Scholar 

  37. Pilon G, Ruzzin J, Rioux LE, Lavigne C, White PJ, Froyland L, Jacques H, Bryl P, Beaulieu L, Marette A (2011) Differential effects of various fish proteins in altering body weight, adiposity, inflammatory status, and insulin sensitivity in high-fat-fed rats. Metabolism 60(8):1122–1130

    Article  CAS  Google Scholar 

  38. Makowski L, Noland RC, Koves TR, Xing W, Ilkayeva OR, Muehlbauer MJ, Stevens RD, Muoio DM (2009) Metabolic profiling of PPAR alpha−/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation. FASEB J 23(2):586–604

    Article  CAS  Google Scholar 

  39. Liu Z, Mutlib AE, Wang J, Talaat RE (2008) Liquid chromatography/mass spectrometry determination of endogenous plasma acetyl and palmitoyl carnitines as potential biomarkers of beta-oxidation in mice. Rapid Commun Mass Spectrom 22(21):3434–3442

    Article  CAS  Google Scholar 

  40. Mandard S, Muller M, Kersten S (2004) Peroxisome proliferator-activated receptor alpha target genes. Cell Mol Life Sci 61(4):393–416

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Kari Williams, Liv Kristine Øysæd, Randi Sandvik, Svein Krüger, and Torunn Eide for excellent technical assistance. We thank Dr. Alfred Halstensen for providing the herring roe and milt. Nofima Biolab Bergen is thanked for performing the lipid analysis on herring roe and milt. This work was supported by grants from NordForsk, grant no. 070010, MitoHealth; EEA Polish-Norwegian Research Fund, grant no. PNRF-104-Al-1/07; the Research Council of Norway, grant no. 190287/110; and the European Community’s Seventh Framework Programme (FP7/2007–2013), grant no. 201668, AtheroRemo.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Medicine, University of Bergen, 5021, Bergen, Norway

    Bodil Bjørndal, Lena Burri, Asbjørn Svardal, Pavol Bohov & Rolf K. Berge

  2. Faculty of Education, Bergen University College, 5020, Bergen, Norway

    Hege Wergedahl

  3. Department of Heart Disease, Haukeland University Hospital, 5021, Bergen, Norway

    Rolf K. Berge

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  1. Bodil Bjørndal
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  2. Lena Burri
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Correspondence to Bodil Bjørndal.

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Bjørndal, B., Burri, L., Wergedahl, H. et al. Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFα. Eur J Nutr 51, 741–753 (2012). https://doi.org/10.1007/s00394-011-0254-8

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  • DOI: https://doi.org/10.1007/s00394-011-0254-8

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