Journal of Obesity & Metabolic Syndrome

Korean Society for the Study of Obesity (대한비만학회)
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Duodenal-Jejunal Bypass Surgery Stimulates the Expressions of Hepatic Sirtuin1 and 3 and Hypothalamic Sirtuin1

  • Ha, Eunyoung (Department of Biochemistry, Keimyung University School of Medicine) ;
  • Kang, Jong Yeon (Department of Biochemistry, Keimyung University School of Medicine) ;
  • Park, Kyung Sik (Department of Biochemistry, Keimyung University School of Medicine) ;
  • Seo, Youn Kyoung (Department of Anatomy and Cell Biology, Hanyang University College of Medicine) ;
  • Ha, Tae Kyung (Department of Surgery, Hanyang University College of Medicine)
  • Received : 2018.07.23
  • Accepted : 2018.12.14
  • Published : 2018.12.30
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Abstract

Background: Sirtuins mediate metabolic responses to nutrient availability and slow aging and accompanying decline in health. This study was designed to assess the expressions of sirtuin1 (SIRT1) and sirtuin3 (SIRT3) in the liver and hypothalamus after duodenal-jejunal bypass (DJB) surgery in rats. Methods: A total of 38 rats were randomly assigned to either sham group (n=8) or DJB group (n=30). DJB group was again divided into three groups according to the elapsed time after surgery (10 weeks, DJB10; 16 week, DJB16; 28 week, DJB28). The mRNA and protein expressions of SIRT1 and SIRT3 in the liver and hypothalamus were measured by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry analyses. $NAD^+/NADH$ ratio was also measured. Results: We found increased mRNA and protein expression levels of SIRT1 in the liver of DJB16 and DJB28 groups compared with those of sham group. The mRNA and protein expressions of SIRT3 in the liver of DJB group increased proportionally to the elapsed time after DJB surgery. The mRNA expression levels of SIRT1 in the hypothalamus increased in DJB16 and DJB28 groups and protein expression levels of SIRT1 in the hypothalamus increased in DJB10, DBJ16, and DJB28 groups compared with sham group. We observed that mRNA and protein levels of SIRT3 in the hypothalamus of DJB group were not changed. Conclusion: This study proves that DJB increases SIRT1 and SIRT3 expressions in the liver and SIRT1 expression in the hypothalamus. These results suggest the possibility of sirtuins being involved in bypass surgery-induced metabolic changes.

Keywords

Acknowledgement

Supported by : Hanyang University

References

  1. Guarente L. Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 2000;14:1021-6.
  2. Haigis MC, Guarente LP. Mammalian sirtuins: emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006;20:2913-21. https://doi.org/10.1101/gad.1467506
  3. Imai S, Johnson FB, Marciniak RA, McVey M, Park PU, Guarente L. Sir2: an NAD-dependent histone deacetylase that connects chromatin silencing, metabolism, and aging. Cold Spring Harb Symp Quant Biol 2000;65:297-302. https://doi.org/10.1101/sqb.2000.65.297
  4. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 1999;13:2570-80. https://doi.org/10.1101/gad.13.19.2570
  5. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 2000;289:2126-8. https://doi.org/10.1126/science.289.5487.2126
  6. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004;305:390-2. https://doi.org/10.1126/science.1099196
  7. Dietrich MO, Antunes C, Geliang G, Liu ZW, Borok E, Nie Y, et al. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 2010;30:11815-25. https://doi.org/10.1523/JNEUROSCI.2234-10.2010
  8. Satoh A, Brace CS, Ben-Josef G, West T, Wozniak DF, Holtzman DM, et al. SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus. J Neurosci 2010;30:10220-32. https://doi.org/10.1523/JNEUROSCI.1385-10.2010
  9. Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michan S, et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metab 2011;14:301-12. https://doi.org/10.1016/j.cmet.2011.06.014
  10. Velasquez DA, Martinez G, Romero A, Vazquez MJ, Boit KD, Dopeso-Reyes IG, et al. The central Sirtuin 1/p53 pathway is essential for the orexigenic action of ghrelin. Diabetes 2011;60:1177-85. https://doi.org/10.2337/db10-0802
  11. Sasaki T, Kim HJ, Kobayashi M, Kitamura YI, Yokota-Hashimoto H, Shiuchi T, et al. Induction of hypothalamic Sirt1 leads to cessation of feeding via agouti-related peptide. Endocrinology 2010;151:2556-66. https://doi.org/10.1210/en.2009-1319
  12. Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci U S A 2002;99:13653-8. https://doi.org/10.1073/pnas.222538099
  13. Green MF, Hirschey MD. SIRT3 weighs heavily in the metabolic balance: a new role for SIRT3 in metabolic syndrome. J Gerontol A Biol Sci Med Sci 2013;68:105-7. https://doi.org/10.1093/gerona/gls132
  14. Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 2011;44:177-90. https://doi.org/10.1016/j.molcel.2011.07.019
  15. Ansari A, Rahman MS, Saha SK, Saikot FK, Deep A, Kim KH. Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease. Aging Cell 2017;16:4-16. https://doi.org/10.1111/acel.12538
  16. Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med 2017;377:1143-55. https://doi.org/10.1056/NEJMoa1700459
  17. Feldman JL, Dittenhafer-Reed KE, Kudo N, Thelen JN, Ito A, Yoshida M, et al. Kinetic and structural basis for acyl-group selectivity and NAD(+) dependence in sirtuin-catalyzed deacylation. Biochemistry 2015;54:3037-50. https://doi.org/10.1021/acs.biochem.5b00150
  18. Jin J, Iakova P, Jiang Y, Medrano EE, Timchenko NA. The reduction of SIRT1 in livers of old mice leads to impaired body homeostasis and to inhibition of liver proliferation. Hepatology 2011;54:989-98. https://doi.org/10.1002/hep.24471
  19. Song YS, Lee SK, Jang YJ, Park HS, Kim JH, Lee YJ, et al. Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes. Diabetes Res Clin Pract 2013;101:341-8. https://doi.org/10.1016/j.diabres.2013.07.002