Fatty acids and immune responses - A new perspective in searching for clues to mechanism

D. Hwang

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Dietary essential fatty acids are the precursors for eicosanoids. Among the eicosanoids derived from arachidonic acid, prostaglandin (PC) E2 is known to possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that the immuno-modulatory roles of dietary fatty acids are mediated at least in part through the alteration of PC biosynthesis. PGs exert their biological effects through their cognate receptors. There are four subtypes of PGE receptors (EP1, EP2, EP3, and EP4) so far identified. Although the association of EP receptors with G proteins coupled to adenylate cyclase and the mobilization of intracellular calcium are well documented, downstream signaling pathways for these receptors are virtually unknown. Identification of downstream signaling pathways for each subtype of EP receptors and target genes regulated by the activation of the receptor will help with our understanding of the mechanism by which dietary fatty acids affect immune responses through the modulation of PGE2 biosynthesis. Emerging evidence suggests that fatty acids can additionally act as second messengers, regulators of signal transducing molecules or transcription factors. Acylation with long-chain fatty acids can occur on a variety of signaling molecules and can affect their membrane translocation and functions. Dietary fatty acids can alter functional properties of lipid mediators by changing the composition of acyl moieties of these molecules. Evidence accumulated recently indicates that long-chain unsaturated fatty acids and their metabolites bind and activate peroxisome proliferator-activated receptors (PPARs). PPARs are nuclear hormone receptors and transcription factors that regulate the expression of broad arrays of genes involved not only in lipid and glucose metabolism, but also in immune and inflammatory responses. PPARs may therefore be important cellular targets that mediate modulation of immune responses by dietary fatty acids. Together, it becomes clear now that multiple steps in various receptor-mediated signaling pathways can be modulated by dietary fatty acids. It will be a challenging task to quantitatively determine how different fatty acids alter functional properties of multitude of signaling components and final cellular responses. Elucidating the mechanism of actions of fatty acids on receptor-mediated signaling pathways in immuno-competent cells will provide a new insight for understanding the immuno-modulatory roles of dietary fatty acids.

Original languageEnglish (US)
Pages (from-to)431-456
Number of pages26
JournalAnnual Review of Nutrition
Volume20
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Fatty Acids
Peroxisome Proliferator-Activated Receptors
Eicosanoids
Dinoprostone
Receptors, Prostaglandin E, EP1 Subtype
Receptors, Prostaglandin E, EP2 Subtype
Transcription Factors
Essential Fatty Acids
Acylation
Second Messenger Systems
Immunosuppressive Agents
Cytoplasmic and Nuclear Receptors
G-Protein-Coupled Receptors
Unsaturated Fatty Acids
Lipid Metabolism
Adenylyl Cyclases
Arachidonic Acid
Transcriptional Activation
Calcium
Lipids

Keywords

  • N-3 fatty acids
  • Peroxisome proliferator-activated receptors
  • Prostaglandin receptors
  • Prostaglandins
  • Receptor-mediated signaling pathways

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Fatty acids and immune responses - A new perspective in searching for clues to mechanism. / Hwang, D.

In: Annual Review of Nutrition, Vol. 20, 2000, p. 431-456.

Research output: Contribution to journalArticle

@article{bfe18462eb494f86b3c5e14c5b552644,
title = "Fatty acids and immune responses - A new perspective in searching for clues to mechanism",
abstract = "Dietary essential fatty acids are the precursors for eicosanoids. Among the eicosanoids derived from arachidonic acid, prostaglandin (PC) E2 is known to possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that the immuno-modulatory roles of dietary fatty acids are mediated at least in part through the alteration of PC biosynthesis. PGs exert their biological effects through their cognate receptors. There are four subtypes of PGE receptors (EP1, EP2, EP3, and EP4) so far identified. Although the association of EP receptors with G proteins coupled to adenylate cyclase and the mobilization of intracellular calcium are well documented, downstream signaling pathways for these receptors are virtually unknown. Identification of downstream signaling pathways for each subtype of EP receptors and target genes regulated by the activation of the receptor will help with our understanding of the mechanism by which dietary fatty acids affect immune responses through the modulation of PGE2 biosynthesis. Emerging evidence suggests that fatty acids can additionally act as second messengers, regulators of signal transducing molecules or transcription factors. Acylation with long-chain fatty acids can occur on a variety of signaling molecules and can affect their membrane translocation and functions. Dietary fatty acids can alter functional properties of lipid mediators by changing the composition of acyl moieties of these molecules. Evidence accumulated recently indicates that long-chain unsaturated fatty acids and their metabolites bind and activate peroxisome proliferator-activated receptors (PPARs). PPARs are nuclear hormone receptors and transcription factors that regulate the expression of broad arrays of genes involved not only in lipid and glucose metabolism, but also in immune and inflammatory responses. PPARs may therefore be important cellular targets that mediate modulation of immune responses by dietary fatty acids. Together, it becomes clear now that multiple steps in various receptor-mediated signaling pathways can be modulated by dietary fatty acids. It will be a challenging task to quantitatively determine how different fatty acids alter functional properties of multitude of signaling components and final cellular responses. Elucidating the mechanism of actions of fatty acids on receptor-mediated signaling pathways in immuno-competent cells will provide a new insight for understanding the immuno-modulatory roles of dietary fatty acids.",
keywords = "N-3 fatty acids, Peroxisome proliferator-activated receptors, Prostaglandin receptors, Prostaglandins, Receptor-mediated signaling pathways",
author = "D. Hwang",
year = "2000",
doi = "10.1146/annurev.nutr.20.1.431",
language = "English (US)",
volume = "20",
pages = "431--456",
journal = "Annual Review of Nutrition",
issn = "0199-9885",
publisher = "Annual Reviews Inc.",

}

TY - JOUR

T1 - Fatty acids and immune responses - A new perspective in searching for clues to mechanism

AU - Hwang, D.

PY - 2000

Y1 - 2000

N2 - Dietary essential fatty acids are the precursors for eicosanoids. Among the eicosanoids derived from arachidonic acid, prostaglandin (PC) E2 is known to possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that the immuno-modulatory roles of dietary fatty acids are mediated at least in part through the alteration of PC biosynthesis. PGs exert their biological effects through their cognate receptors. There are four subtypes of PGE receptors (EP1, EP2, EP3, and EP4) so far identified. Although the association of EP receptors with G proteins coupled to adenylate cyclase and the mobilization of intracellular calcium are well documented, downstream signaling pathways for these receptors are virtually unknown. Identification of downstream signaling pathways for each subtype of EP receptors and target genes regulated by the activation of the receptor will help with our understanding of the mechanism by which dietary fatty acids affect immune responses through the modulation of PGE2 biosynthesis. Emerging evidence suggests that fatty acids can additionally act as second messengers, regulators of signal transducing molecules or transcription factors. Acylation with long-chain fatty acids can occur on a variety of signaling molecules and can affect their membrane translocation and functions. Dietary fatty acids can alter functional properties of lipid mediators by changing the composition of acyl moieties of these molecules. Evidence accumulated recently indicates that long-chain unsaturated fatty acids and their metabolites bind and activate peroxisome proliferator-activated receptors (PPARs). PPARs are nuclear hormone receptors and transcription factors that regulate the expression of broad arrays of genes involved not only in lipid and glucose metabolism, but also in immune and inflammatory responses. PPARs may therefore be important cellular targets that mediate modulation of immune responses by dietary fatty acids. Together, it becomes clear now that multiple steps in various receptor-mediated signaling pathways can be modulated by dietary fatty acids. It will be a challenging task to quantitatively determine how different fatty acids alter functional properties of multitude of signaling components and final cellular responses. Elucidating the mechanism of actions of fatty acids on receptor-mediated signaling pathways in immuno-competent cells will provide a new insight for understanding the immuno-modulatory roles of dietary fatty acids.

AB - Dietary essential fatty acids are the precursors for eicosanoids. Among the eicosanoids derived from arachidonic acid, prostaglandin (PC) E2 is known to possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that the immuno-modulatory roles of dietary fatty acids are mediated at least in part through the alteration of PC biosynthesis. PGs exert their biological effects through their cognate receptors. There are four subtypes of PGE receptors (EP1, EP2, EP3, and EP4) so far identified. Although the association of EP receptors with G proteins coupled to adenylate cyclase and the mobilization of intracellular calcium are well documented, downstream signaling pathways for these receptors are virtually unknown. Identification of downstream signaling pathways for each subtype of EP receptors and target genes regulated by the activation of the receptor will help with our understanding of the mechanism by which dietary fatty acids affect immune responses through the modulation of PGE2 biosynthesis. Emerging evidence suggests that fatty acids can additionally act as second messengers, regulators of signal transducing molecules or transcription factors. Acylation with long-chain fatty acids can occur on a variety of signaling molecules and can affect their membrane translocation and functions. Dietary fatty acids can alter functional properties of lipid mediators by changing the composition of acyl moieties of these molecules. Evidence accumulated recently indicates that long-chain unsaturated fatty acids and their metabolites bind and activate peroxisome proliferator-activated receptors (PPARs). PPARs are nuclear hormone receptors and transcription factors that regulate the expression of broad arrays of genes involved not only in lipid and glucose metabolism, but also in immune and inflammatory responses. PPARs may therefore be important cellular targets that mediate modulation of immune responses by dietary fatty acids. Together, it becomes clear now that multiple steps in various receptor-mediated signaling pathways can be modulated by dietary fatty acids. It will be a challenging task to quantitatively determine how different fatty acids alter functional properties of multitude of signaling components and final cellular responses. Elucidating the mechanism of actions of fatty acids on receptor-mediated signaling pathways in immuno-competent cells will provide a new insight for understanding the immuno-modulatory roles of dietary fatty acids.

KW - N-3 fatty acids

KW - Peroxisome proliferator-activated receptors

KW - Prostaglandin receptors

KW - Prostaglandins

KW - Receptor-mediated signaling pathways

UR - http://www.scopus.com/inward/record.url?scp=0033835309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033835309&partnerID=8YFLogxK

U2 - 10.1146/annurev.nutr.20.1.431

DO - 10.1146/annurev.nutr.20.1.431

M3 - Article

VL - 20

SP - 431

EP - 456

JO - Annual Review of Nutrition

JF - Annual Review of Nutrition

SN - 0199-9885

ER -