Transcript No Slide Title

Long chain polyunsaturated fatty
acids and inflammation
Philip Calder
Professor of Nutritional Immunology
University of Southampton
Rolling
BLOODSTREAM
Adhesion
Diapedesis
Inflammatory
Chemoattractants cytokines Vasoactive
mediators
Systemic effects
(incl. inflammation)
Local
injury
Inflammatory cytokines
Inflammatory eicosanoids
Reactive species
TISSUE
Activated
leukocyte
Calder et al. (2009) Brit. J. Nutr. 101, S1-S45
Diseases or conditions that
involve inflammation
Rheumatoid arthritis
Crohn’s disease
Ulcerative colitis
Cystic fibrosis
Psoriasis
Lupus
Type-1 diabetes
Childhood asthma
Adult asthma
Allergic diseases
Atopic diseases
COPD
Atherosclerosis
Acute cardiovascular events
Response to surgery
Trauma & sepsis
Neurodegenerative diseases
Some cancers
Body wasting
Obesity …….
What have fatty acids got to do with
inflammation?
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Fatty acid nutrition could influence
metabolite and/or hormone concentrations
that in turn influence inflammation
 Fatty acid nutrition could influence other
factors (e.g. oxidised LDL; oxidative stress)
that in turn influence inflammation
 Direct pro- or anti-inflammatory effects via
surface or intracellular “fatty acid receptors”
 Effects mediated via changes in
inflammatory cell membrane phospholipids
=> Fatty acids differentially affect
inflammation/immunity via cell surface (TLR4,
GPR120) and intracellular (PPAR-g) receptors
Altered
fatty acid supply
Altered composition
of inflammatory cell phospholipids
Membrane
alterations: rafts; order;
trafficking
Signal transduction
pathways leading
to gene expression
Altered inflammatory cell phenotype
Altered inflammatory response
Lipid mediators
Fish oil-derived long chain w-3 PUFAs
exert anti-inflammatory effects by
inhibiting production of arachidonic
acid-derived eicosanoids
EPA is also a substrate for
eicosanoid synthesis
Arachidonic acid
2-series PGs
4-series LTs
“STRONG”
EPA
3-series PGs
5-series LTs
“WEAK”
w-3 fatty acid exposure
Receptors
Membrane composition
Raft assembly
Fluidity
Substrates for
eicosanoids,
resolvins etc.
Signals
Cell responses
Altered (patho)physiology
(less inflammatory phenotype)
Summary
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Inflammation underlies many common conditions and
diseases
Fatty acids can influence inflammation acting through cell
surface and intracellular receptors/sensors that control
inflammatory gene expression
Human inflammatory cells typically contain a relatively high
amount of arachidonic acid -> precursor of inflammatory
eicosanoids
w-3 PUFAs from fish oil are readily incorporated into
inflammatory cells
Fatty acid composition of inflammatory cells affects
membrane fluidity, membrane raft formation, signal
transduction processes leading to gene expression, and the
pattern of lipid and peptide mediators produced
Through these effects fatty acids can affect inflammatory cell
responses and inflammatory processes
Fish oil (w-3 PUFAs) exerts anti-inflammatory actions in vivo
that may be associated with improved patient outcome
Conclusions
Fatty acid composition of inflammatory cells influences their function
Arachidonic acid, EPA and DHA contents seem to be important
Mechanisms by which fatty acids affect inflammation are many and
complex
Long chain w-3 PUFAs are anti-inflammatory
There is a theoretical basis, supported by much pre-clinical science,
for clinical benefit from increased long chain w-3 PUFA supply in
various patient groups
Dose (of w-3 fatty acid) is important