Fatty acids – from energy substrates to key regulators of cell survival, proliferation and effector function
Authors:Danilo Cucchi1, Dolores Camacho-Muñoz2, Michelangelo Certo3, Valentina Pucino3, Anna Nicolaou2,4 and Claudio Mauro3,5,6
1 Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
2 Laboratory for Lipidomics and Lipid Biology, Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, School of Health sciences, The University of Manchester, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PT, UK.
3 Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK.
4 Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9PT, UK.
5 Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK.
6 Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK.
Keywords:
fatty acids; immune cells; T cells; cancer cells; metastasis; cancer immunology.
Abbreviatons:
ACC – acetyl-CoA carboxylase,
ACLY – ATP citrate lyase,
CPT – carnitine palmitoyl transferases,
CRPC – castration-resistant prostate cancer,
DHA – docosahexaenoic acid,
EAE – experimental autoimmune encephalomyelitis,
EMT – epithelial to mesenchymal transition, EPA – eicosapentaenoic acid,
FABP – Fatty acid binding protein,
FADS – fatty acyl-CoA desaturase,
FAS – fatty acid synthase,
GA – gastric adenocarcinoma,
HCC – hepatocellular carcinoma,
HDAC – histone deacetylase,
HFD – high fat diet,
ILC – innate lymphoid cell,
LAL – lysosomal acid lipase,
LMW-E – low molecular weight isoform of cyclin E,
LPS – lipopolysaccharide,
mCRPC – metastatic CRCP,
NK – natural killer,
PI(4,5)P2 – phosphatidylinositol (4,5) bisphosphate,
PLD – phospholipase D,
PPAR – peroxisome proliferator-activated receptor,
PUFA – polyunsaturated fatty acid,
SCD – stearoyl-CoA desaturase,
SREBP – sterol regulatory element binding protein,
Tconv – conventional T cell,
TCR – T cell receptor,
Teff – T effector cell,
Th – T helper cell,
Tm – T memory cell, TNBC – triple-negative breast cancer,
Treg – regulatory T cell,
wt – wild type.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Please cite this article as:
Danilo Cucchi, Dolores Camacho-Muñoz, Michelangelo Certo, Valentina Pucino, Anna Nicolaou and Claudio Mauro (2019). Fatty acids - from energy substrates to key regu-lators of cell survival, proliferation and effector function. Cell Stress 4(1): 9-23. doi: 10.15698/cst2020.01.209
© 2019 Cucchi et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
Recent advances in immunology and cancer research show that fatty acids, their metabolism and their sensing have a crucial role in the biology of many different cell types. Indeed, they are able to affect cellular behaviour with great implications for pathophysiology. Both the catabolic and anabolic pathways of fatty acids present us with a number of enzymes, receptors and agonists/antagonists that are potential therapeutic targets, some of which have already been successfully pursued. Fatty acids can affect the differentiation of immune cells, particularly T cells, as well as their activation and function, with important consequences for the balance between anti- and pro-inflammatory signals in immune diseases, such as rheumatoid arthritis, psoriasis, diabetes, obesity and cardiovascular conditions. In the context of cancer biology, fatty acids mainly provide substrates for energy production, which is of crucial importance to meet the energy demands of these highly proliferating cells. Fatty acids can also be involved in a broader transcriptional programme as they trigger signals necessary for tumorigenesis and can confer to cancer cells the ability to migrate and generate distant metastasis. For these reasons, the study of fatty acids represents a new research direction that can generate detailed insight and provide novel tools for the understanding of immune and cancer cell biology, and, more importantly, support the development of novel, efficient and fine-tuned clinical interventions. Here, we review the recent literature focusing on the involvement of fatty acids in the biology of immune cells, with emphasis on T cells, and cancer cells, from sensing and binding, to metabolism and downstream effects in cell signalling.