Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Chathyan Pararasa, John Ikwuobe, Shahjahan Shigdar, Alexis Boukouvalas, Ian T. Nabney, James E. Brown, Andrew Devitt, Clifford J. Bailey, Stuart J. Bennett, Helen R. Griffiths

Research output: Contribution to journalArticle

Abstract

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Original languageEnglish
Pages (from-to)128-139
Number of pages12
JournalAging Cell
Volume15
Issue number1
Early online date2 Nov 2015
DOIs
Publication statusPublished - Feb 2016

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Peroxisome Proliferator-Activated Receptors
Monocytes
Fatty Acids
Ceramides
Macrophages
Cytokines
Glutathione Disulfide
Oxidative Phosphorylation
Tetradecanoylphorbol Acetate
Unsaturated Fatty Acids
Lipid Metabolism
Gas Chromatography
Interleukin-10
Linear Models
Interleukin-6
Leukocytes
Anti-Inflammatory Agents
Inflammation
Phenotype

Bibliographical note

© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding: BBSRC

Keywords

  • anti-inflammatory
  • macrophage
  • mitochondrial ROS
  • oleate
  • oxidative phosphorylation
  • palmitate

Cite this

Pararasa, Chathyan ; Ikwuobe, John ; Shigdar, Shahjahan ; Boukouvalas, Alexis ; Nabney, Ian T. ; Brown, James E. ; Devitt, Andrew ; Bailey, Clifford J. ; Bennett, Stuart J. ; Griffiths, Helen R. / Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ. In: Aging Cell. 2016 ; Vol. 15, No. 1. pp. 128-139.
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Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ. / Pararasa, Chathyan; Ikwuobe, John; Shigdar, Shahjahan; Boukouvalas, Alexis; Nabney, Ian T.; Brown, James E.; Devitt, Andrew; Bailey, Clifford J.; Bennett, Stuart J.; Griffiths, Helen R.

In: Aging Cell, Vol. 15, No. 1, 02.2016, p. 128-139.

Research output: Contribution to journalArticle

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AU - Pararasa, Chathyan

AU - Ikwuobe, John

AU - Shigdar, Shahjahan

AU - Boukouvalas, Alexis

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AU - Devitt, Andrew

AU - Bailey, Clifford J.

AU - Bennett, Stuart J.

AU - Griffiths, Helen R.

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