Skip to main content
SpringerLink
Log in

Hepatic lipid accumulation is ameliorated in obese KK mice by dietary sei whale oil

  • Original Article
  • Chemistry and Biochemistry
  • Published:
Fisheries Science Aims and scope Submit manuscript

Abstract

Whale oil (WO) contains n-3 polyunsaturated fatty acids (PUFAs), but the effects of whale oil intake on lipid metabolism have remained unclear. We examined the influence of WO on lipid metabolism in obese KK mice. Male KK mice were fed a high-fat diet for 12 weeks to induce obesity. The mice were then given free access to a different diet for 10 weeks: the lard/safflower oil (LSO) diet consisted of 25 energy% (en%) LSO (6:4), the WO diet consisted of 25 en% WO, and the fish oil (FO) diet consisted of 11 en% FO plus 14 en% LSO. The n-3 PUFA content of the FO diet was the same as that in the WO diet. In the WO and FO groups, the total plasma cholesterol level was significantly decreased compared with that in the LSO group. The number of lipid droplets in liver specimens was also lower in the WO and FO groups, and the hepatic triglyceride and total cholesterol levels were decreased in these groups compared with the LSO group. Hepatic mRNA levels of fatty acid synthase, and stearoyl-CoA desaturase 1, which are fatty acid synthesis-related genes, were decreased in the WO and FO groups. No significant differences were observed between the WO and FO groups. Taken together, these results indicate that WO intake inhibits lipid accumulation in the liver by reducing fatty acid biosynthesis.

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

Similar content being viewed by others

Abbreviations

ACC:

Acyl-coA carboxylase

AOX:

Acyl-CoA oxidase

CPT:

Carnitine palmitoyltransferase

CT:

Computed tomography

CYP7A1:

Cholesterol 7 α-hydroxylase

DHA:

Docosahexaenoic acid

DPA:

Docosapentaenoic acid

d-ROM:

Diacron of reactive oxygen metabolites

ELISA:

Enzyme-linked immunosorbent assay

EPA:

Icosapentaenoic acid

FAS:

Fatty acid synthase

FO:

Fish oil

GK:

Glucokinase

HE:

Hematoxylin-eosin

HDL:

High-density lipoprotein

HMG-CoA:

3-Hydroxy-3-methylglutaryl-coenzyme A

LSO:

Lard/safflower oil

MCAD:

Medium-chain acyl-CoA dehydrogenase

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

NEFA:

Non-esterified fatty acid

PCR:

Polymerase chain reaction

PEPCK:

Phosphoenolpyruvate carboxykinase

PPAR:

Peroxisome proliferator-activated receptor

PUFA:

Polyunsaturated fatty acid

SCD:

Stearoyl-CoA desaturase

SREBP:

Sterol regulatory element-binding protein

U.CARR:

Carratelli units

UCP:

Uncoupling protein

WAT:

White adipose tissue

WO:

Whale oil

References

  1. Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB (2002) Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 162:1867–1872

    Article  PubMed  Google Scholar 

  2. Gotto AM Jr (1998) Triglyceride: the forgotten risk factor. Circulation 97:1027–1028

    Article  PubMed  Google Scholar 

  3. Meshkani R, Adeli K (2009) Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem 42:1331–1346

    Article  CAS  PubMed  Google Scholar 

  4. Contos MJ, Sanyal AJ (2002) The clinicopathologic spectrum and management of nonalcoholic fatty liver disease. Adv Anat Pathol 9:37–51

    Article  PubMed  Google Scholar 

  5. Goldberg IJ, Ginsberg HN (2006) Ins and outs modulating hepatic triglyceride and development of nonalcoholic fatty liver disease. Gastroenterology 130:1343–1346

    Article  CAS  PubMed  Google Scholar 

  6. Dyerberg J, Bang HO (1979) Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 2:433–435

    Article  CAS  PubMed  Google Scholar 

  7. Dyerberg J, Bang HO, Hjorne N (1975) Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 28:958–966

    CAS  PubMed  Google Scholar 

  8. Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR (1978) Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 2:117–119

    Article  CAS  PubMed  Google Scholar 

  9. Bang HO, Dyerberg J, Sinclair HM (1980) The composition of the Eskimo food in north western Greenland. Am J Clin Nutr 33:2657–2661

    CAS  PubMed  Google Scholar 

  10. Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K et al (2006) Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 113:195–202

    Article  CAS  PubMed  Google Scholar 

  11. Mozaffarian D, Rimm EB (2006) Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296:1885–1899

    Article  CAS  PubMed  Google Scholar 

  12. Yamagishi K, Iso H, Date C, Fukui M, Wakai K et al (2008) Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol 52:988–996

    Article  CAS  PubMed  Google Scholar 

  13. Nestel PJ (1990) Effects of N-3 fatty acids on lipid metabolism. Annu Rev Nutr 10:149–167

    Article  CAS  PubMed  Google Scholar 

  14. Halminski MA, Marsh JB, Harrison EH (1991) Differential effects of fish oil, safflower oil and palm oil on fatty acid oxidation and glycerolipid synthesis in rat liver. J Nutr 121:1554–1561

    CAS  PubMed  Google Scholar 

  15. Ide T, Kobayashi H, Ashakumary L, Rouyer IA, Takahashi Y et al (2000) Comparative effects of perilla and fish oils on the activity and gene expression of fatty acid oxidation enzymes in rat liver. Biochim Biophys Acta 1485:23–35

    Article  CAS  PubMed  Google Scholar 

  16. Kim H, Takahashi M, Ezaki O (1999) Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs. J Biol Chem 274:25892–25898

    Article  CAS  PubMed  Google Scholar 

  17. Tsuboyama-Kasaoka N, Takahashi M, Kim H, Ezaki O (1999) Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or fibrate administration in mice. Biochem Biophys Res Commun 257:879–885

    Article  CAS  PubMed  Google Scholar 

  18. Hofacer R, Magrisso IJ, Jandacek R, Rider T, Tso P et al (2012) Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: positive association with non-fasting plasma triglyceride levels. Prostaglandins Leukot Essent Fatty Acids 86:71–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nakatani T, Tsuboyama-Kasaoka N, Takahashi M, Miura S, Ezaki O (2002) Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes. J Biol Chem 277:9562–9569

    Article  CAS  PubMed  Google Scholar 

  20. Nakatani T, Kim H, Kaburagi Y, Yasuda K, Ezaki O (2003) A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity. J Lipid Res 44:369–379

    Article  CAS  PubMed  Google Scholar 

  21. Xu J, Teran-Garcia M, Park JH, Nakamura MT, Clarke SD (2001) Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay. J Biol Chem 276:9800–9807

    Article  CAS  PubMed  Google Scholar 

  22. Ou J, Tu H, Shan B, Luk A, DeBose-Boyd RA et al (2001) Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR. Proc Natl Acad Sci USA 98:6027–6032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hirako S, Kim H, Arai T, Chiba H, Matsumoto A (2010) Effect of concomitantly used fish oil and cholesterol on lipid metabolism. J Nutr Biochem 21:573–579

    Article  CAS  PubMed  Google Scholar 

  24. Hirako S, Kim H, Iizuka Y, Nakasatomi M, Matsumoto A (2013) Fish oil prevents excessive hepatic lipid accumulation without inducing oxidative stress. Prostaglandins Leukot Essent Fatty Acids 88:365–371

    Article  CAS  PubMed  Google Scholar 

  25. Hirako S, Kim H, Shimizu S, Chiba H, Matsumoto A (2011) Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice. J Agric Food Chem 59:13353–13359

    Article  CAS  PubMed  Google Scholar 

  26. Arai T, Kim H, Hirako S, Nakasatomi M, Chiba H et al (2013) Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity. J Nutr Biochem 24:267–273

    Article  CAS  PubMed  Google Scholar 

  27. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    CAS  PubMed  Google Scholar 

  28. Arai T, Kim HJ, Chiba H, Matsumoto A (2009) Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice. J Atheroscler Thromb 16:674–683

    Article  CAS  PubMed  Google Scholar 

  29. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW et al (2006) Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 55:924–928

    Article  CAS  PubMed  Google Scholar 

  30. Okanoue T, Umemura A, Yasui K, Itoh Y (2011) Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in Japan. J Gastroenterol Hepatol Suppl 1:153–162

    Article  Google Scholar 

  31. Rodriguez VM, Portillo MP, Pico C, Macarulla MT, Palou A (2002) Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle. Am J Clin Nutr 75:213–220

    CAS  PubMed  Google Scholar 

  32. Soriguer F, Rojo-Martinez G, de Fonseca FR, Garcia-Escobar E, Garcia Fuentes E et al (2007) Obesity and the metabolic syndrome in Mediterranean countries: a hypothesis related to olive oil. Mol Nutr Food Res 51:1260–1267

    Article  CAS  PubMed  Google Scholar 

  33. Deng X, Elam MB, Wilcox HG, Cagen LM, Park EA et al (2004) Dietary olive oil and menhaden oil mitigate induction of lipogenesis in hyperinsulinemic corpulent JCR:LA-cp rats: microarray analysis of lipid-related gene expression. Endocrinology 145:5847–5861

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank NOF Corporation (Tokyo, Japan) for providing FO. This study was supported in part by Grant-in-Aid for Scientific Research on Innovative Areas (to S.S., Grant No. 22126004) and Grant-in-Aid for Young Scientists (B) (to S.H., Grant No. 90644261) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Department of Health and Nutrition, University of Human Arts and Sciences, Saitama, Japan

    Satoshi Hirako

  2. Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan

    Mamiko Suzuki, Satoru Yamanaka & Akira Miyazaki

  3. Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan

    Hyounju Kim, Yuzuru Iizuka & Akiyo Matsumoto

  4. Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Nobuhiro Wada

  5. Tokyo Shokuryo Dietitian Academy, Tokyo, Japan

    Mai Okabe

  6. Department of Exercise and Sports Physiology, School of Pharmacy and Pharmaceutical Science, Hoshi University, Tokyo, Japan

    Fumiko Takenoya

  7. The Institute of Cetacean Research, Tokyo, Japan

    Genta Yasunaga

  8. School of Pharmacy and Pharmaceutical Sciences, Global Research Center for Innovative Life Science Peptide Drug Innovation, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Seiji Shioda

Authors
  1. Satoshi Hirako
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mamiko Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyounju Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuzuru Iizuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akiyo Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobuhiro Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mai Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fumiko Takenoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Genta Yasunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Satoru Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Akira Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Seiji Shioda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seiji Shioda.

Ethics declarations

Conflict of interest

This study was funded by Kyodo Senpaku Kaisha, Ltd, Tokyo, Japan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hirako, S., Suzuki, M., Kim, H. et al. Hepatic lipid accumulation is ameliorated in obese KK mice by dietary sei whale oil. Fish Sci 82, 509–517 (2016). https://doi.org/10.1007/s12562-016-0971-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12562-016-0971-2

Keywords

Search

Navigation