Elsevier

Nutrition

Volume 41, September 2017, Pages 90-96
Nutrition

Review
Nutrigenomics of ω-3 fatty acids: Regulators of the master transcription factors

https://doi.org/10.1016/j.nut.2017.04.012Get rights and content

Highlights

  • ω-3 fatty acids (O3 FAs) work as metabolic regulators.

  • O3 FAs modulate signal transduction throughout the cell membranes.

  • O3 FAs control the expression of master transcriptional factors.

  • NF-κB, SREBP, PPARs, and ChREBP are master transcriptional factors regulated by O3 FA.

  • NF-κB regulates gene transcription of proteins involved in inflammation.

Abstract

It is well known that ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) control some key molecular cell mechanisms, resulting in a beneficial role in inflammatory diseases. Such mechanisms are complex and reflect the diversity of their functions, mainly as modulators of the dynamic properties of membranes, regulators of gene expression, and precursors of active mediators. The aim of this review is to summarize the state of the art of the effects and mechanisms by which ω-3 LC-PUFAs such as eicosapentaenoic acid (EPA, C22:5 ω-3) and docosahexaenoic acid (DHA, C22:6 ω-3) regulate different metabolic processes to maintain homeostasis. Thus, we describe some aspects of these fatty acids—from their structural function in cell membranes to their role as regulators of gene expression, mainly in lipid metabolism. However, further studies are required to elucidate these actions and to have a better understanding in regard to the beneficial effects of ω-3 LC-PUFAs in the pathogenesis of several diseases as well as their functions as nutrients with protective action to avoid or delay development of these diseases. Furthermore, it is necessary to highlight the lack of comprehensive studies including nutritional, biochemical, genetic, and immune aspects to identify specific molecular mechanisms involved in the beneficial effects of consumption of DHA (C22:6 ω-3) and EPA (C22:5 ω-3) and their metabolic derivatives on health promotion.

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)

  • M. Rodríguez-Cruz et al.

    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

    (2011)
  • M. Rodríguez-Cruz et al.

    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

    (2012)
  • R.S. González et al.

    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

    (2014)
  • Y. Qin et al.

    Regulation of hepatic fatty acid elongase 5 by LXRalpha-SREBP-1 c

    Biochim Biophys Acta

    (2009)
  • M. Sekiya et al.

    Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression

    Hepatology

    (2003)
  • J. Xu et al.

    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

    (1999)
  • D. Botolin et al.

    Docosahexaneoic acid (22:6, n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26 S proteasome-dependent pathways

    J Lipid Res

    (2006)
  • J. Xu et al.

    Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay

    J Biol Chem

    (2001)
  • T. Varga et al.

    PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation

    Biochim Biophys Acta

    (2011)
  • W.A. Alaynick

    Nuclear receptors, mitochondria and lipid metabolism

    Mitochondrion

    (2008)
  • E.D. Rosen et al.

    PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro

    Mol Cell

    (1999)
  • J.N. Feige et al.

    From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions

    Prog Lipid Res

    (2006)
  • T.-C. He et al.

    PPAR delta is an APC-regulated target of nonsteroidal anti-inflammatory drugs

    Cell

    (1999)
  • O.A. Gani et al.

    Molecular recognition of docosahexaenoic acid by peroxisome proliferator-activated receptors and retinoid-X receptor alpha

    J Mol Graph Model

    (2008)
  • D.B. Jump et al.

    Docosahexaenoic acid (DHA) and hepatic gene transcription

    Chem Phys Lipids

    (2008)
  • S.D. Clarke et al.

    Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors

    Am J Clin Nutr

    (1999)
  • A.K. Stoeckman et al.

    Mlx is the functional heteromeric partner of the carbohydrate response element-binding protein in glucose regulation of lipogenic enzyme genes

    J Biol Chem

    (2004)
  • H.M. Shih et al.

    Two CACGTG motifs with proper spacing dictate the carbohydrate regulation of hepatic gene transcription

    J Biol Chem

    (1995)
  • T. Kawaguchi et al.

    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

    (2002)
  • J. Xu et al.

    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

    (2006)
  • R. Sen et al.

    Multiple nuclear factors interact with the immunoglobulin enhancer sequences

    Cell

    (1986)
  • C.J. Lo et al.

    Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity

    J Surg Res

    (1999)
  • M. López-Alarcón et al.

    Supplementation of n3 long-chain polyunsaturated fatty acid synergically decrease insulin resistance with weight loss of obese prepubertal and pubertal children

    Arch Med Res

    (2011)
  • M. Bernabe-García et al.

    Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence

    Prostaglandins Leukot Essent Fatty Acids

    (2011)
  • A. Palou et al.

    Nutrigenómica y obesidad

    Biologia (Bratisl)

    (2004)
  • C. Gladine et al.

    Nutrigenomic effects of omega-3 fatty acids

    Lipid Technol

    (2014)
  • M.D. Mesa et al.

    Importancia de los lípidos en el tratamiento nutricional de las patologías de base inflamatoria

    Nutr Hosp

    (2006)
  • K. Je

    Food lipids and fatty acids: Importance in food quality, nutrition and health

    Food Technol

    (1988)
  • Cited by (0)

    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.

    View full text