Cell Biochemistry and Biophysics

, Volume 59, Issue 2, pp 89–97 | Cite as

Molecular Mechanisms by Which Saturated Fatty Acids Modulate TNF-α Expression in Mouse Macrophage Lineage

  • Thais Martins de Lima-SalgadoEmail author
  • Tatiana C. Alba-Loureiro
  • Caroline S. do Nascimento
  • Maria T. Nunes
  • Rui Curi
Original Research


Many macrophage functions are modulated by fatty acids (FAs), including cytokine release, such as tumor necrosis factor-α (TNF-α). TNF-α is of great interest due to its role in the inflammation process observed in several diseases such as rheumatoid arthritis, atherosclerosis, and obesity. However, the mechanisms by which FA effects occur have not been completely elucidated yet. In this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect of 50 and 100 μM of saturated (palmitic and stearic acids), monounsaturated (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-α production. Alterations in gene expression, poly(A) tail length and activation of transcription factors were evaluated. Oleic and linoleic acids, usually known as neutral or pro-inflammatory FA, inhibited LPS-induced TNF-α secretion by the cells. Saturated FAs were potent inducers of TNF-α expression and secretion under basal and inflammatory conditions (in the presence of LPS). Although the effect of the saturated FA was similar, the mechanism involved in each case seem to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and stearic acid increased mRNA poly(A) tail. These results may contribute to the understanding of the molecular mechanisms by which saturated FAs modulate the inflammatory response and may lead to design of associations of dietary and pharmacological strategies to counteract the pathological effects of TNF-α.


Saturated fatty acid TNF-α Gene expression Poly(A) tail Transcription factors 



Fatty acid




Early growth response 1


cAMP responsive element binding


Nuclear factor kappa B


Activator protein


Controlled amino acid therapy (CAAT)/enhancer binding protein


Fetal calf serum


Palmitic acid


Stearic acid


Oleic acid


Linoleic acid


Reverse transcriptase-polymerase chain reaction


β-2 microglobulin


Moloney murine leukemia virus


Rapid amplification of cDNA ends


Polyadenylation tail


Electrophoretic mobility shift assay


Polynucleotide kinase


Toll-like receptor





The authors are grateful to the technical assistance of G. de Souza, J. R. Mendonça, and E. P. Portioli. This research is supported by FAPESP, CNPq, and CAPES.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Thais Martins de Lima-Salgado
    • 1
    Email author
  • Tatiana C. Alba-Loureiro
    • 2
  • Caroline S. do Nascimento
    • 3
  • Maria T. Nunes
    • 3
  • Rui Curi
    • 2
  1. 1.Laboratory of Clinical Emergency (LIM51), Emergency Medicine Department, Medical SchoolUniversity of São PauloSão PauloBrazil
  2. 2.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  3. 3.Department of Physiology and Biophysics, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil

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