ReviewNutrigenomics of ω-3 fatty acids: Regulators of the master transcription factors
Introduction
The importance of nutrigenomics resides in the actual knowledge about the interactions between genes and their functional products with nutrients in the development of certain diseases [1]. Dietary components can alter gene expression directly or indirectly, showing a beneficial or harmful physiological effect.
The foods we consume daily contain thousands of biologically active substances, many of which have the potential to provide substantial health benefits. Among these benefits are those related to polyunsaturated fatty acids (PUFAs). The discovery that PUFAs can act as ligands of transcription factors indicates that these fatty acids (FAs) are not merely passive molecules that provide energy, but also work as metabolic regulators [2]. Through dietary studies, PUFAs and, especially long-chain (LC)-PUFAs such as docosahexaenoic acid (DHA, C22:6 ω-3), have been positively related to a variety of human diseases including cancer, rheumatoid arthritis, asthma, lupus erythematosus, depression, respiratory diseases, dermatitis, psoriasis, and cystic fibrosis. For a simple molecule such as DHA, diverse processes can be affected, which apparently have no correlation. However, a common fundamental function in most cells may be the inflammatory process [3], [4], [5].
This review summarizes the state of the art of the effects and mechanisms by which ω-3 LC-PUFAs and their derivatives regulate key genes of metabolic processes within cells and tissues in the organism to maintain homeostasis. We describe some relevant and actual aspects of these FAs, from their structural function in cell membranes to their role as regulators of gene expression, mainly in lipid metabolism. With this information, we attempt to provide a better understanding about the beneficial role of ω-3 LC-PUFAs to comprehend the action of these FAs in the pathogenesis of several diseases.
Section snippets
Functions of PUFAS
ω-3 LC-PUFAs such as eicosapentaenoic acid (EPA, C22:5 ω-3) or DHA are synthesized de novo in the organism from the essential polyunsaturated fatty α-linolenic acid ω-3 (C18:3 ω-3) or acquired from the diet. Cellular function regulation by these FAs can occur at different levels such as modulation of signal transduction by the bioactive effect over the cell membranes and regulation of gene transcription, among others.
Conclusions
A molecular and harmonic mechanism exists within the organism where ω-3 LC-PUFAs regulate cell functions, mainly by modulating signal transduction through the effect of PUFA bioactivity over cell membranes and the regulation of gene transcription to maintain cellular homeostasis. It is well known that ω-3 LC-PUFAs control many key molecular mechanisms in the cell such as lipid and carbohydrate metabolism and inflammation through master transcriptional regulators. However, further studies are
Acknowledgment
The authors acknowledge Sharon Morey, Scientific Communications, for providing editorial assistance.
References (76)
- et al.
Docosahexaenoic acid domains: the ultimate non-raft membrane domain
Chem Phys Lipids
(2008) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance
Biochim Biophys Acta
(2015)Mechanisms of action of (n-3) fatty acids
J Nutr
(2012)- et al.
Oleic and docosahexaenoic acid differentially phase separate from lipid raft molecules: a comparative NMR, DSC, AFM, and detergent extraction study
Biophys J
(2004) - et al.
Effect of the long-term feeding of dietary lipids on the learning ability, fatty acid composition of brain stem phospholipids and synaptic membrane fluidity in adult mice: a comparison of sardine oil diet with palm oil diet
Mech Ageing Dev
(1998) - et al.
Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants
Am J Clin Nutr
(1994) - et al.
Intrauterine fatty acid accretion rates in human brain: Implications for fatty acid requirements
Early Hum Dev
(1980) - et al.
Synthesis of long-chain polyunsaturated fatty acids in lactating mammary gland: role of Delta 5 and Delta 6 desaturases, SREBP-1, PPARalpha, and PGC-1
J Lipid Res
(2006) - et al.
The effect of gestational age on expression of genes involved in uptake, trafficking and synthesis of fatty acids in the rat placenta
Gene
(2016) - et al.
Fatty acid regulation of gene transcription
J Nutr
(2005)
Participation of mammary gland in the long-chain polyunsaturated fatty acid synthesis during pregnancy and lactation: Role of srebp-1 c desaturases and elongases
Biochim Biophys Acta
Coexisting role of fasting or feeding and dietary lipids in the control of gene expression of enzymes involved in the synthesis of saturated, monounsaturated and polyunsaturated fatty acids
Gene
Role of maternal tissue in the synthesis of polyunsaturated fatty acids in response to a lipid-deficient diet during pregnancy and lactation in rats
Gene
Regulation of hepatic fatty acid elongase 5 by LXRalpha-SREBP-1 c
Biochim Biophys Acta
Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression
Hepatology
Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats
J Biol Chem
Docosahexaneoic acid (22:6, n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26 S proteasome-dependent pathways
J Lipid Res
Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay
J Biol Chem
PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation
Biochim Biophys Acta
Nuclear receptors, mitochondria and lipid metabolism
Mitochondrion
PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro
Mol Cell
From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions
Prog Lipid Res
PPAR delta is an APC-regulated target of nonsteroidal anti-inflammatory drugs
Cell
Molecular recognition of docosahexaenoic acid by peroxisome proliferator-activated receptors and retinoid-X receptor alpha
J Mol Graph Model
Docosahexaenoic acid (DHA) and hepatic gene transcription
Chem Phys Lipids
Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors
Am J Clin Nutr
Mlx is the functional heteromeric partner of the carbohydrate response element-binding protein in glucose regulation of lipogenic enzyme genes
J Biol Chem
Two CACGTG motifs with proper spacing dictate the carbohydrate regulation of hepatic gene transcription
J Biol Chem
Mechanism for fatty acid “sparing” effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase
J Biol Chem
Regulation of rat hepatic L-pyruvate kinase promoter composition and activity by glucose, n-3 polyunsaturated fatty acids, and peroxisome proliferator-activated receptor-a agonist
J Biol Chem
Multiple nuclear factors interact with the immunoglobulin enhancer sequences
Cell
Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity
J Surg Res
Supplementation of n3 long-chain polyunsaturated fatty acid synergically decrease insulin resistance with weight loss of obese prepubertal and pubertal children
Arch Med Res
Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence
Prostaglandins Leukot Essent Fatty Acids
Nutrigenómica y obesidad
Biologia (Bratisl)
Nutrigenomic effects of omega-3 fatty acids
Lipid Technol
Importancia de los lípidos en el tratamiento nutricional de las patologías de base inflamatoria
Nutr Hosp
Food lipids and fatty acids: Importance in food quality, nutrition and health
Food Technol
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This study was supported by the Consejo Nacional de Ciencia y Tenologia (CONACYT) México (Grant #SALUD-2012-01-180058). MRC participated in the conception of the review; analysis of the data published; and drafting, revision, and approval of the final version of the manuscript. DSS contributed to the literature search, analysis of the data published, and writing of the manuscript. The authors have no conflicts of interest to declare.