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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
?? 50811700Jl ??
College of Engineering & Physical Sciences > Systems analytics research institute (SARI)
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 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
Uncontrolled Keywords: anti-inflammatory,macrophage,mitochondrial ROS,oleate,oxidative phosphorylation,palmitate,Cell Biology,Ageing
Publication ISSN: 1474-9726
Last Modified: 17 Jun 2024 07:18
Date Deposited: 08 Oct 2015 13:40
Full Text Link: http://onlineli ... .12416/abstract
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2016-02
Published Online Date: 2015-11-02
Accepted Date: 2015-09-23
Authors: Pararasa, Chathyan
Ikwuobe, John
Shigdar, Shahjahan
Boukouvalas, Alexis
Nabney, Ian T. (ORCID Profile 0000-0003-1513-993X)
Brown, James E. (ORCID Profile 0000-0002-3504-7373)
Devitt, Andrew (ORCID Profile 0000-0002-4651-6761)
Bailey, Clifford J. (ORCID Profile 0000-0002-6998-6811)
Bennett, Stuart J.
Griffiths, Helen R. (ORCID Profile 0000-0002-2666-2147)



Version: Published Version

License: Creative Commons Attribution

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