Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis

Na Young Song, Yeon Hwa Lee, Hye Kyung Na, Jeong Heum Baek, Young Joon Surh

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD + -dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells. Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis. Leptin-induced SIRT1 expression was regulated by the redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2). Leptin stimulated nuclear accumulation of Nrf2 as well as its binding to the antioxidant response elements located in the SIRT1 promoter. Moreover, siRNA knockdown of Nrf2 abrogated the leptin-induced SIRT1 expression. Notably, SIRT1 was significantly reduced in colon tissues of Nrf2-null mice, lending further support to Nrf2-dependent SIRT1 expression. Expression of leptin, Nrf2 and SIRT1 was coordinately increased in human colon tumor tissues. In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression.

Original languageEnglish
Pages (from-to)282-291
Number of pages10
JournalBiochemical Pharmacology
Volume153
DOIs
Publication statusPublished - 2018 Jul

Bibliographical note

Funding Information:
This work was supported by a Global Core Research Center grant from the National Research Foundation, Republic of Korea (Grant No. 2011-003-0001).

Funding Information:
This work was supported by a Global Core Research Center grant from the National Research Foundation, Republic of Korea (Grant No. 2011-003-0001 ).

Publisher Copyright:
© 2018 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Fingerprint

Dive into the research topics of 'Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis'. Together they form a unique fingerprint.

Cite this