Evolutionary conservation of metabolism explains howDrosophila nutrigenomics can help us understand human nutrigenomics

While large populations in the third world are enduring famine, much of the developed world is undergoing an obesity epidemic. In addition to reflecting an unbalanced distribution of food, the "epidemic of overabundance" is ironically leading to a decrease in the health and longevity of the obese and improperly nourished in the first world. International consortia, such as the European Nutrigenomics Organization (NuGO), are increasing our knowledge of nutrientgene interactions and the effects of diet and obesity on human health. In this review, we summarize both previous and ongoing nutrigenomics studies in Drosophila and we explain how these studies can be used to provide insights into molecular mechanisms underlying nutrigenomics in humans. We will discuss how quantitative trait locus (QTL) experiments have identified genes that affect triglyceride levels in Drosophila, and how microarray analyses show that hundreds of genes have altered gene expression under different dietary conditions. Finally, we will discuss ongoing combined microarray-QTL studies, termed "genetical genomics," that promise to identify "master modulatory loci" that regulate global responses of potentially hundreds of genes under different dietary conditions. When "master modulatory loci" are identified in Drosophila, then experiments in mammalian models can be used to determine the relevance of these genes to human nutrition and health.     

The opposing effects of n-3 and n-6 fatty acids

Polyunsaturated fatty acids (PUFAs) can be classified in n-3 fatty acids and n-6 fatty acids, and in westernized diet the predominant dietary PUFAs are n-6 fatty acids. Both types of fatty acids are precursors of signaling molecules with opposing effects, that modulate membrane microdomain composition, receptor signaling and gene expression. The predominant n-6 fatty acid is arachidonic acid, which is converted to prostaglandins, leukotrienes and other lipoxygenase or cyclooxygenase products. These products are important regulators of cellular functions with inflammatory, atherogenic and prothrombotic effects. Typical n-3 fatty acids are docosahexaenoic acid and eicosapentaenoic acid, which are competitive substrates for the enzymes and products of arachidonic acid metabolism. Docosahexaenoic acid- and eicosapentaenoic acid-derived eicosanoids antagonize the pro-inflammatory effects of n-6 fatty acids. n-3 and n-6 fatty acids are ligands/modulators for the nuclear receptors NFkappaB, PPAR and SREBP-1c, which control various genes of inflammatory signaling and lipid metabolism. n-3 Fatty acids down-regulate inflammatory genes and lipid synthesis, and stimulate fatty acid degradation. In addition, the n-3/n-6 PUFA content of cell and organelle membranes, as well as membrane microdomains strongly influences membrane function and numerous cellular processes such as cell death and survival.     

Nutrigenomics: a case study in the measurement of insect response to nutritional quality

Recent developments in the area of nutrigenomics hold the promise of providing valuable information about the impact of nutrition on a wide range of biochemical parameters by investigating how nutrition alters global gene expression patterns. Our goal is to use a nutrigenomics approach to identify insect molecular markers that could be used as early indicators of insect responses to different nutritional sources. Such molecular markers could be chosen for degree of expression and evaluated for suitability as nutritional biomarkers by examining developmental and generational expression. Ideal markers would be highly expressed, manifested in the first generation within one developmental stage, and consistent over many generations. Our objective for the current study was to illustrate the potential discovery of molecular markers using Perillus bioculatus (F.) (Heteroptera: Pentatomidae), when reared on an optimal vs. suboptimal diet, and analyze the presence of differentially expressed genes resulting from those treatments. In this paper we present preliminary results of microarray and subtractive hybridization experiments that represent the feasibility of using nutrigenomics to assist in analyzing insect responses to nutritional changes and dietary quality with the intent of stimulating further studies in this area.     

Understanding the nutrigenomic definitions and concepts at the food-genome junction

The marked differences in individual response to dietary factors have led to major controversies in nutrition and puzzled nutrition scientists over the last century. The emerging field of nutrigenomics helps us to understand the basis for some of these differences and also promises us the ability to tailor diet based on individual genetic makeup. Great advances in Human Genome Project, documentation of single nucleotide polymorphisms (SNPs) in candidate genes and their association with metabolic imbalances have gradually added new tests to the nutrigenomic panel. Studies based on ethnopharmacology and phytotherapy concepts showed that nutrients and botanicals can interact with the genome causing marked changes in gene expression. This has led to the commercial development of nutraceuticals and functional foods that can modify negative health effects of individual genetic profile bringing the field to the "food/genome" junction. Despite the promise of nutrigenomics to personalize diet, there is skepticism whether it can truly bring about meaningful modification of the risk factors connected to chronic diseases, due to the lack of large scale nutrition intervention studies. Several intervention studies currently underway in the United States and abroad (Israel, Spain, and France) will further help validate nutrigenomic concepts. France has already introduced a National Nutrition and Health Program to assess nutritional status and risk of major metabolic diseases. As the field(s) related to nutritional genomics advance in their scope, it is essential that: (a) strict guidelines be followed in the nomenclature and definition of the subdisciplines; and (b) the state/federal regulatory guidelines be updated for diagnostic laboratories, especially for those offering tests directly to the public (without a physician's request) to help protect the consumer.     

Role of nuclear receptors in the regulation of gene expression by dietary fatty acids (review)

Long chain fatty acids, derived either from endogenous metabolism or by nutritional sources play significant roles in important biological processes of membrane structure, production of biologically active compounds, and participation in cellular signaling processes. Recently, the structure of dietary fatty acids has become an important issue in human health because ingestion of saturated fats (containing triglycerides composed of saturated fatty acids) is considered harmful, while unsaturated fats are viewed as beneficial. It is important to note that the molecular reason for this dichotomy still remains elusive. Since fatty acids are important players in development of pathology of cardiovascular and endocrine system, understanding the key molecular targets of fatty acids, in particular those that discriminate between saturated and unsaturated fats, is much needed. Recently, insights have been gained on several fatty acid-activated nuclear receptors involved in gene expression. In other words, we can now envision long chain fatty acids as regulators of signal transduction processes and gene regulation, which in turn will dictate their roles in health and disease. In this review, we will discuss fatty acid-mediated regulation of nuclear receptors. We will focus on peroxisome proliferators-activated receptors (PPARs), liver X receptors (LXR), retinoid X receptors (RXRs), and Hepatocyte Nuclear Factor alpha (HNF-4alpha), all of which play pivotal roles in dietary fatty acid-mediated effects. Also, the regulation of gene expression by Conjugated Linoleic Acids (CLA), a family of dienoic fatty acids with a variety of beneficial effects, will be discussed.     

Nutrigenomics and nutrigenetics

PURPOSE OF REVIEW: Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutritional genomics covers nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome, and nutrigenetics, the major goal of which is to elucidate the effect of genetic variation on the interaction between diet and disease. Nutrigenetics has been used for decades in certain rare monogenic diseases such as phenylketonuria, and it has the potential to provide a basis for personalized dietary recommendations based on the individual's genetic makeup in order to prevent common multifactorial disorders decades before their clinical manifestation. RECENT FINDINGS: Preliminary results regarding gene-diet interactions in cardiovascular diseases are for the most part inconclusive because of the limitations of current experimental designs. Success in this area will require the integration of various disciplines, and will require investigators to work on large population studies that are designed to investigate gene-environment interactions. SUMMARY: Based on the current knowledge, we anticipate that in the future we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes, with nutrition being the cornerstone of this endeavor.     

Nutrigenomics: integrating genomic approaches into nutrition research

It has been suggested that the supermarket of today will be the pharmacy of tomorrow. Such statements have been derived from recognition of our increasing ability to optimize nutrition, and maintain a state of good health through longer periods of life. The new field of nutrigenomics, which focuses on the interaction between bioactive dietary components and the genome, recognizes that current nutritional guidelines may be ideal for only a relatively small proportion of the population. There is good evidence that nutrition has significant influences on the expression of genes, and, likewise, genetic variation can have a significant effect on food intake, metabolic response to food, individual nutrient requirements, food safety, and the efficacy of disease-protective dietary factors. For example, a significant number of human studies in various areas are increasing the evidence for interactions between single nucleotide polymorphisms (SNPs) in various genes and the metabolic response to diet, including the risk of obesity. Many of the same genetic polymorphisms and dietary patterns that influence obesity or cardiovascular disease also affect cancer, since overweight individuals are at increased risk of cancer development. The control of food intake is profoundly affected by polymorphisms either in genes encoding taste receptors or in genes encoding a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. Total dietary intake, and the satiety value of various foods, will profoundly influence the effects of these genes. Identifying key SNPs that are likely to influence the health of an individual provides an approach to understanding and, ultimately, to optimizing nutrition at the population or individual level. Traditional methods for identification of SNPs may involve consideration of individual variants, using methodologies such as restriction fragment length polymorphisms or quantitative real-time PCR assays. New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches.     

营养基因组学的研究进展

伴随着基因组学、生物信息学等的迅猛发展及其在生命科学领域的应用,营养基因组学应运而生,并迅速成为营养学研究的新前沿。营养基因组学主要研究营养素和植物化学物质对人体基因的转录、翻译表达以及代谢机制,其可能的应用范围包括营养素作用的分子机制、营养素的人体需要量、个体食谱的制定以及食品安全等。本文重点介绍营养基因组学的研究内容与现状,并对今后的研究趋势作了展望。     

Ethical, legal and social issues in nutrigenomics: the challenges of regulating service delivery and building health professional capacity

Nutrigenomics, the conjunction of molecular nutrition with human genomics, is among the first publicly available applications of the human genome project. Nutrigenomics raises ethical, legal and social issues particularly with respect to how the public may access nutrigenetic tests and associated nutritional and lifestyle advice. Current regulatory controversy focuses on potential harms associated with direct-to-consumer (DTC) marketing of nutrigenetic tests and especially the need to protect consumers from unreliable tests, false claims and unproven dietary supplements. Nutrigenomics does, however, offer the potential of important health benefits for some individuals. The regulation of nutrigenomic services is slowly evolving, but there is little indication of increased professional capacity to support service delivery. Primary care physicians have minimal training in nutrition and genetics, and medical geneticists are in high demand and short supply. Dietetic practitioners are experts in nutrition science and interest in nutrigenomics is growing among members of this professional group. However, as with physicians, dietetics practitioners would require considerable training to bring nutrigenomics into their practice capacity. A downside of regulatory restrictions on direct consumer access to nutrigenomics companies is that responsible businesses may be hindered in meeting emergent public demand while health care professional groups have not yet developed capacity to provide nutrigenomics services.     

Nutrigenomics of hepatic steatosis in a feline model: effect of monosodium glutamate, fructose, and Trans-fat feeding

Nonalcoholic fatty liver disease begins with a relatively benign hepatic steatosis, often associated with increased adiposity, but may progress to a more severe nonalcoholic steatohepatitis with inflammation. A subset of these patients develops progressive fibrosis and ultimately cirrhosis. Various dietary components have been shown to contribute to the development of liver disease, including fat, sugars, and neonatal treatment with high doses of monosodium glutamate (MSG). However, rodent models of progressive disease have been disappointing, and alternative animal models of diet-induced liver disease would be desirable, particularly if they contribute to our knowledge of changes in gene expression as a result of dietary manipulation. The domestic cat has previously been shown to be an appropriate model for examining metabolic changes–associated human diseases such as diabetes. Our aim was therefore to compare changes in hepatic gene expression induced by dietary MSG, with that of a diet containing Trans-fat and high fructose corn syrup (HFCS), using a feline model. MSG treatment increased adiposity and promoted hepatic steatosis compared to control (P < 0.05). Exposure to Trans-fat and HFCS promoted hepatic fibrosis and markers of liver dysfunction. Affymetrix microarray analysis of hepatic gene expression showed that dietary MSG promoted the expression of genes involved in cholesterol and steroid metabolism. Conversely, Trans-fat and HFCS feeding promoted the expression of genes involved in lipolysis, glycolysis, liver damage/regeneration, and fibrosis. Our feline model examining gene–diet interactions (nutrigenomics) demonstrates how dietary MSG, Trans-fat, and HFCS may contribute to the development of hepatic steatosis.