Elsevier

Nutrition

Volume 20, Issue 1, January 2004, Pages 103-108
Nutrition

Lipid metabolism
Nutrigenomic approach to understanding the mechanisms by which dietary long-chain fatty acids induce gene signals and control mechanisms involved in carcinogenesis

https://doi.org/10.1016/j.nut.2003.09.018Get rights and content

Introduction

Nutrigenomic approaches are enhancing our understanding of how dietary lipids affect cell signaling and carcinogenesis. Novel technologies such as microarrays and Serial Analysis of Gene Expression (SAGE) allow the simultaneous measurement of mRNA expression levels of hundreds or thousands of genes. These are the forerunner genomic technologies currently being applied to nutrition; however, they are increasingly being combined with other global analytical emerging strategies including proteomics and metabolomics.

Lipids are components of most foods. Aside from their principal dietary role of delivering energy to the body, dietary lipids are involved in normal and aberrant mitogenic processes and have been linked to the development and progression of colon cancer, colon carcinogenesis, hepatocarcinogenesis, breast cancer, and mammary carcinogenesis and metastasis. Lipids influence multiple signaling pathways involved in disease progression, some of which are difficult to study with a single gene, protein, or biomarker approach. Therefore, the mechanisms by which lipids influence cancer are for the large part unknown, partly due to the lack of research tools that can adequately cover the complex mechanisms involved.

Long-chain polyunsaturated fatty acids (LC-PUFA) are probably the most commonly studied dietary lipids with respect to their effects on carcinogenesis. The effects of diets high in LC-PUFA have been studied for decades. Bougnoux1 extensively reviewed the influence of LC-PUFAs on cancer and carcinogenesis. The inhibitory effects of fish oil, which is rich in ω-3 LC-PUFA, on carcinogenesis have been shown in various models including an azoxymethane-induced rat colon carcinogenesis model and an HT29 colon tumor growth and metastasis nude mouse model.2, 3 Although cell culture and animal studies support a preventive action of LC-PUFA, there is divided opinion on the association between LC-PUFA intake and cancer risk in humans. For example, case control, international comparisons, and animal studies have suggested an association between fat intake and breast cancer incidence, but cohort studies have not reported this association.4

Recent studies have applied nutrigenomic approaches to better elucidate the complex cell regulation processes affected by LC-PUFAs.5, 6, 7 In this review we describe a few selected mechanisms through which LC-PUFA can affect carcinogenesis and then review studies that used a nutrigenomics approach to study LC-PUFA effects on carcinogenesis.

Section snippets

Biological and carcinogenic effects of LC-PUFA

Processes affected by dietary LC-PUFA consumption include growth; neurologic development; lean and fat mass accretions; reproduction; innate and acquired immunities; infectious pathologies of viruses, bacteria, and parasites; and the incidence and severity of virtually all chronic and degenerative diseases including cancer, atherosclerosis, stroke, arthritis, diabetes, osteoporosis, and neurodegenerative, inflammatory, and skin diseases.8, 9, 10, 11 There is a distinct difference between the

Relevance of microarrays to assess the influence of lipids on cell regulation

Genomics technologies have changed the strategy of nutrition research. It is now possible to measure simultaneously thousands of biological events in molecular detail.66 Scientists are now extending the analysis of gene expression and its global perspective to examine the other layers of biological organization, i.e., proteins and metabolites.67 Unfortunately, lipid metabolic pathway information has been discouragingly underdeveloped with respect to genes, proteins, and regulatory elements.

The

Outlook

Continued use of “-omic” approaches, namely genomics, proteomics, and metabolomics, will dramatically increase our understanding of how dietary lipids affect carcinogenesis, leading to healthier foods. Driven by the rapid progress in genomics, the enormous task of cataloging, cross-referencing, and database organization for massive biological data sets is now being tackled by academia and the private sector. These advances in information management have enabled a conceptual shift in the

Acknowledgements

The authors thank David Mutch for his contribution to the literature search and Dr. Mark Waldron for his careful review of our manuscript. They also thank Prof. Bruce German for his insight and inspiration in the field of lipid nutrition.

First page preview

First page preview
Click to open first page preview

References (75)

  • J.M. Walker et al.

    Endocannabinoids in pain modulation

    Prostaglandins Leukot Essent Fatty Acids

    (2002)
  • R.K. Amer et al.

    A lipoxygenase product, hepoxilin A(3), enhances nerve growth factor-dependent neurite regeneration post-axotomy in rat superior cervical ganglion neurons in vitro

    Neuroscience

    (2003)
  • C.J. Chu et al.

    N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia

    J Biol Chem

    (2003)
  • S.A. Kliewer et al.

    The nuclear receptor PPARgamma—bigger than fat

    Curr Opin Genet Dev

    (1998)
  • H. Sprecher

    Metabolism of highly unsaturated n-3 and n-6 fatty acids

    Biochim Biophys Acta

    (2000)
  • F.J. Gonzalez

    The peroxisome proliferator-activated receptor alpha (PPARalpha)role in hepatocarcinogenesis

    Mol Cell Endocrinol

    (2002)
  • K.L. Houseknecht et al.

    Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligandsa review

    Domest Anim Endocrinol

    (2002)
  • R.A. Gupta et al.

    Target genes of peroxisome proliferator-activated receptor gamma in colorectal cancer cells

    J Biol Chem

    (2001)
  • K.M. Suchanek et al.

    Peroxisome proliferator-activated receptor beta expression in human breast epithelial cell lines of tumorigenic and non-tumorigenic origin

    Int J Biochem Cell Biol

    (2002)
  • Y.Y. Fan et al.

    Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts

    J Nutr

    (2003)
  • J.Y. Lee et al.

    Docosahexaenoic acid suppresses the activity of peroxisome proliferator-activated receptors in a colon tumor cell line

    Biochem Biophys Res Commun

    (2002)
  • T. Nakatani et al.

    A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liverrelationship to anti-obesity

    J Lipid Res

    (2003)
  • Y.A. Yang et al.

    Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

    Exp Cell Res

    (2003)
  • Y.A. Yang et al.

    Activation of fatty acid synthesis during neoplastic transformationrole of mitogen-activated protein kinase and phosphatidylinositol 3-kinase

    Exp Cell Res

    (2002)
  • M.A. Roberts et al.

    Genomicsfood and nutrition

    Curr Opin Biotech

    (2001)
  • J.B. German et al.

    Metabolomics and individual metabolic assessmentthe next great challenge for nutrition

    J Nutr

    (2002)
  • P. Bougnoux

    [Polyunsaturated fatty acids and cancer]

    Rev Prat

    (2000)
  • P.C. Calder et al.

    Dietary fish oil suppresses human colon tumour growth in athymic mice

    Clin Sci (Lond)

    (1998)
  • W.C. Willett

    Diet and breast cancer

    J Intern Med

    (2001)
  • B.A. Narayanan et al.

    Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells

    Int J Oncol

    (2001)
  • A. Berger et al.

    Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression

    Lipids Health Dis

    (2002)
  • B.A. Narayanan et al.

    Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells

    Cancer Res

    (2003)
  • D. Volker et al.

    Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis

    J Rheumatol

    (2000)
  • F.B. Hu et al.

    Fish and omega-3 fatty acid intake and risk of coronary heart disease in women

    JAMA

    (2002)
  • D.Y. Kim et al.

    Stimulatory effects of high-fat diets on colon cell proliferation depend on the type of dietary fat and site of the colon

    Nutr Cancer

    (1998)
  • D. Bagga et al.

    Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion

    Proc Natl Acad Sci USA

    (2003)
  • A.R. Heller et al.

    Fish or chips?

    News Physiol Sci

    (2003)
  • Cited by (32)

    • Cloning and expressions of peroxisome proliferator activated receptor alpha1 and alpha2 (PPARα1 and PPARα2) in loach (Misgurnus anguillicaudatus) and in response to different dietary fatty acids

      2016, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      As important dietary lipid resource, fish oil is rich in n-3 long-chain polyunsaturated fatty acids (LC-PUFAs), while soybean oil contains more n-6 PUFA (especially linoleic acid) [11]. Moreover, studies showed that the bindings of n-3 PUFA (rich in FO) and their oxidized fatty acid derivatives to PPARα contributed to reduce liver triglyceride content, which functioned by suppressing lipogenesis coordinately and promoting fatty acid oxidation [30,31]. In this way, stimulating the expressions of carnitine palmitoyltransferase (CPT) and peroxisomal acyl-CoA oxidase contributed to PPARα expression.

    • Foodomics: Food science and nutrition in the postgenomic era

      2014, Comprehensive Analytical Chemistry
      Citation Excerpt :

      Two conceptually different analytical approaches have emerged to allow quantitative and comprehensive analysis of changes in mRNA expression levels of hundreds or thousands of genes. One approach is based on microarray technology (9,11,12) and the other group of techniques is based on DNA sequencing (13). DNA microarrays are collections of oligonucleotides or probes, representing thousands of genes, attached to a substrate, usually a glass slide, at predefined locations within a grid pattern.

    • Nutritional genomics and personalized diet

      2011, Egyptian Journal of Medical Human Genetics
      Citation Excerpt :

      Cancer is a process composed of multiple stages in which gene expression, and protein and metabolite function begin to operate aberrantly [36]. In the post-genomic era, the cellular events mediating the onset of carcinogenesis, in addition to their modulation by dietary factors, has yielded important information in understanding of this disease [37]. Inherited mutations in genes can increase one’s susceptibility for cancer.

    • Putting the 'Ome' in lipid metabolism

      2006, Biotechnology Annual Review
      Citation Excerpt :

      Indeed, unraveling the metabolic events following the consumption of nutritional compounds via an integrated approach has the potential to characterize molecular targets that will lead to improved personalized dietary recommendations [12,71]. One of the most widely debated issues in nutrition regards the addition of arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) into infant formula; despite the beneficial roles of long-chain polyunsaturated fatty acids (LC-PUFA) on health status having been repeatedly demonstrated [72]. Based on previous findings, it could be assumed that a predominant role of DHA is to simply antagonize AA-mediated events [73,74]; however, a recent study demonstrated that hepatic stearoyl-CoA desaturase (SCD) is a specific target for AA, and that this novel mechanism of action is neither synergized nor attenuated by the addition of a DHA-enriched fish oil, indicating unique actions for each LC-PUFA [66].

    View all citing articles on Scopus

    The Medic Foundation and Nestlé supported this work.

    View full text