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Down-Regulation of Hepatic Stearoyl-CoA Desaturase-1 Expression by Fucoxanthin via Leptin Signaling in Diabetic/Obese KK-A y Mice

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Lipids

Abstract

Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A y and leptin-deficiency ob/ob. In KK-A y mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A y mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A y mice but not in leptin-deficient ob/ob mice.

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Abbreviations

SCD:

Stearoyl-coenzyme A desaturase

mRNA:

Messenger RNA

18:0:

Stearic acid

18:1n-9:

Oleic acid

WAT:

White adipose tissue

PCR:

Polymerase chain reaction

References

  1. Hosokawa M, Miyashita T, Nishikawa S, Emi S, Tsukui T, Beppu F, Okada T, Miyashita K (2010) Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic/obese KK-Ay mice. Arch Biochem Biophys 504:17–25

    Article  PubMed  CAS  Google Scholar 

  2. Tsukui T, Konno K, Hosokawa M, Maeda H, Sashima T, Miyashita K (2007) Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese/diabetic mice. J Agric Food Chem 55:5025–5029

    Article  PubMed  CAS  Google Scholar 

  3. Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99:11482–11486

    Article  PubMed  CAS  Google Scholar 

  4. Miyazaki M, Kim YC, Gray-Keller MP, Attie AD, Ntambi JM (2000) The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of the gene for stearoyl-CoA desaturase 1. J Biol Chem 275:30132–30138

    Article  PubMed  CAS  Google Scholar 

  5. Kaestner KH, Ntambi JM, Kelly TJ Jr, Lane MD (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem 264:14755–14761

    PubMed  CAS  Google Scholar 

  6. Bjermo H, Risérus U (2010) Role of hepatic desaturases in obesity-related metabolic disorders. Curr Opin Clin Nutr Metab Care 13:703–708

    Article  PubMed  CAS  Google Scholar 

  7. Miyazaki M, Bruggink SM, Ntambi JM (2006) Identification of mouse palmitoyl-coenzyme A Delta9-desaturase. J Lipid Res 47:700–704

    Article  PubMed  CAS  Google Scholar 

  8. Ntambi JM, Miyazaki M (2003) Recent insights into stearoyl-CoA desaturase-1. Curr Opin Lipidol 14:255–261

    Article  PubMed  CAS  Google Scholar 

  9. Jiang G, Li Z, Liu F, Ellsworth K, Dallas-Yang Q, Wu M, Ronan J, Esau C, Murphy C, Szalkowski D, Bergeron R, Doebber T, Zhang BB (2005) Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J Clin Invest 115:1030–1038

    PubMed  CAS  Google Scholar 

  10. Miyazaki M, Sampath H, Liu X, Flowers MT, Chu K, Dobrzyn A, Ntambi JM (2009) Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice. Biochem Biophys Res Commun 380:818–822

    Article  PubMed  CAS  Google Scholar 

  11. Gautron L, Elmquist JK (2011) Sixteen years and counting: an update on leptin in energy balance. J Clin Invest 121:2087–2093

    Article  PubMed  CAS  Google Scholar 

  12. Myers MG, Cowley MA, Münzberg H (2008) Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 70:537–556

    Article  PubMed  CAS  Google Scholar 

  13. Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM, Friedman JM (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297:240–243

    Article  PubMed  CAS  Google Scholar 

  14. Maeda H, Hosokawa M, Sashima T, Funayama K, Miyashita K (2005) Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem Biophys Res Commun 332:392–397

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Prevot AF, Mordret FX (1976) Utilisation des colonnes capillaries de verre pour l’analyse des corps gras par chromotographie en phase gazeuse. Rev Fse Corps Gras 23:409–423 (in French)

    CAS  Google Scholar 

  17. Masuzaki H, Ogawa Y, Aizawa-Abe M, Hosoda K, Suga J, Ebihara K, Satoh N, Iwai H, Inoue G, Nishimura H, Yoshimasa Y, Nakao K (1999) Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes. Diabetes 48:1615–1622

    Article  PubMed  CAS  Google Scholar 

  18. Nishikawa S, Hosokawa M, Miyashita K (2012) Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A y mice. Phytomedicine 19:389–394

    Article  PubMed  CAS  Google Scholar 

  19. Flowers JB, Rabaglia ME, Schueler KL, Flowers MT, Lan H, Keller MP, Ntambi JM, Attie AD (2007) Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. Diabetes 56:1228–1239

    Article  PubMed  CAS  Google Scholar 

  20. Rahman SM, Dobrzyn A, Dobrzyn P, Lee SH, Miyazaki M, Ntambi JM (2003) Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. Proc Natl Acad Sci USA 100:11110–11115

    Article  PubMed  CAS  Google Scholar 

  21. Rahman SM, Dobrzyn A, Lee SH, Dobrzyn P, Miyazaki M, Ntambi JM (2005) Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue. Am J Physiol Endocrinol Metab 288:E381–E387

    Article  PubMed  CAS  Google Scholar 

  22. Woo MN, Jeon SM, Kim HJ, Lee MK, Shin SK, Shin YC, Park YB, Choi MS (2010) Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL/6 N mice. Chem Biol Interact 186:316–322

    Article  PubMed  CAS  Google Scholar 

  23. Mauvoisin D, Prévost M, Ducheix S, Arnaud MP, Mounier C (2010) Key role of the ERK1/2 MAPK pathway in the transcriptional regulation of the stearoyl-CoA desaturase (SCD1) gene expression in response to leptin. Mol Cell Endocrinol 319:116–128

    Article  PubMed  CAS  Google Scholar 

  24. Biddinger SB, Miyazaki M, Boucher J, Ntambi JM, Kahn CR (2006) Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 55:2032–2041

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (M.H., 23380120) and by the Japan Society for the Promotion of Science (JSPS) Grant-in Aid for JSPS Fellows (F.B., 2867).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Fisheries Sciences, Hokkaido University, 3-1-1, Minato-cho, Hakodate, Hokkaido, 041-8611, Japan

    Fumiaki Beppu, Masashi Hosokawa, Mi-Jin Yim, Taro Shinoda & Kazuo Miyashita

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  1. Fumiaki Beppu
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  2. Masashi Hosokawa
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  3. Mi-Jin Yim
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  4. Taro Shinoda
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  5. Kazuo Miyashita
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Correspondence to Masashi Hosokawa.

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Beppu, F., Hosokawa, M., Yim, MJ. et al. Down-Regulation of Hepatic Stearoyl-CoA Desaturase-1 Expression by Fucoxanthin via Leptin Signaling in Diabetic/Obese KK-A y Mice. Lipids 48, 449–455 (2013). https://doi.org/10.1007/s11745-013-3784-4

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  • DOI: https://doi.org/10.1007/s11745-013-3784-4

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