SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes

Takeshi Yoshizaki, Jill C. Milne, Takeshi Imamura, Simon Schenk, Noriyuki Sonoda, Jennie Bever, Juu Chin Lu, Jesse J. Smith, Michael R. Jirousek, Jerrold M. Olefsky

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

SIRT1 is a prominent member of a family of NAD+-dependent enzymes and affects a variety of cellular functions ranging from gene silencing, regulation of the cell cycle and apoptosis, to energy homeostasis. In mature adipocytes, SIRT1 triggers lipolysis and loss of fat content. However, the potential effects of SIRT1 on insulin signaling pathways are poorly understood. To assess this, we used RNA interference to knock down SIRT1 in 3T3-L1 adipocytes. SIRT1 depletion inhibited insulin-stimulated glucose uptake and GLUT4 translocation. This was accompanied by increased phosphorylation of JNK and serine phosphorylation of insulin receptor substrate 1 (IRS-1), along with inhibition of insulin signaling steps, such as tyrosine phosphorylation of IRS-1, and phosphorylation of Akt and ERK. In contrast, treatment of cells with specific small molecule SIRT1 activators led to an increase in glucose uptake and insulin signaling as well as a decrease in serine phosphorylation of IRS-1. Moreover, gene expression profiles showed that SIRT1 expression was inversely related to inflammatory gene expression. Finally, we show that treatment of 3T3-L1 adipocytes with a SIRT1 activator attenuated tumor necrosis factor alpha-induced insulin resistance. Taken together, these data indicate that SIRT1 is a positive regulator of insulin signaling at least partially through the anti-inflammatory actions in 3T3-L1 adipocytes.

Original languageEnglish (US)
Pages (from-to)1363-1374
Number of pages12
JournalMolecular and Cellular Biology
Volume29
Issue number5
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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Adipocytes
Insulin Resistance
Anti-Inflammatory Agents
Insulin Receptor Substrate Proteins
Phosphorylation
Insulin
Serine
Glucose
Lipolysis
Gene Silencing
RNA Interference
Transcriptome
NAD
Tyrosine
Cell Cycle
Homeostasis
Tumor Necrosis Factor-alpha
Fats
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yoshizaki, T., Milne, J. C., Imamura, T., Schenk, S., Sonoda, N., Bever, J., ... Olefsky, J. M. (2009). SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Molecular and Cellular Biology, 29(5), 1363-1374. https://doi.org/10.1128/MCB.00705-08

SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. / Yoshizaki, Takeshi; Milne, Jill C.; Imamura, Takeshi; Schenk, Simon; Sonoda, Noriyuki; Bever, Jennie; Lu, Juu Chin; Smith, Jesse J.; Jirousek, Michael R.; Olefsky, Jerrold M.

In: Molecular and Cellular Biology, Vol. 29, No. 5, 01.03.2009, p. 1363-1374.

Research output: Contribution to journalArticle

Yoshizaki, T, Milne, JC, Imamura, T, Schenk, S, Sonoda, N, Bever, J, Lu, JC, Smith, JJ, Jirousek, MR & Olefsky, JM 2009, 'SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes', Molecular and Cellular Biology, vol. 29, no. 5, pp. 1363-1374. https://doi.org/10.1128/MCB.00705-08
Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Bever J et al. SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Molecular and Cellular Biology. 2009 Mar 1;29(5):1363-1374. https://doi.org/10.1128/MCB.00705-08
Yoshizaki, Takeshi ; Milne, Jill C. ; Imamura, Takeshi ; Schenk, Simon ; Sonoda, Noriyuki ; Bever, Jennie ; Lu, Juu Chin ; Smith, Jesse J. ; Jirousek, Michael R. ; Olefsky, Jerrold M. / SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 5. pp. 1363-1374.
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