Nutrition and Gene Regulation Symposium Introduction : Nutrition and Gene Regulation 1

Nutritional genomics is the study of nutrient-gene interactions and the effect these interactions have on health. It includes how diet affects the way genes are expressed, the effect of genes on how the body uses nutrients, and the effects of nutrients on molecular level processes in the body. It is an area of science that seeks to help people improve their health by studying how genes influence responses of genetically similar individuals or groups to foods. Knowledge of these interactions and variations can then be applied in the field of nutrigenetics to improve dietary guidelines for populations, or to tailor-make specific diets for individuals. Dietary patterns are known to be strongly linked to 7 of the top 10 causes of sickness and death in North America, including heart disease, obesity, several cancers, and diabetes. A diet practiced by one individual may support his or her health and quality of life, yet the same diet practiced by another may lead to obesity and subsequent metabolic problems that compromise quality of life. The science of nutritional genomics should increase our understanding of diet-health-gene interactions, and provide a number of potential benefits for individuals, groups, and societies. These include improved individual health, greater consumer choice and control, an increased role for prevention in health management, greater social equity, and health care savings through the prevention and slowing of diseases. However, translating the flood of information from the mapping of the human genome into useful knowledge is a slow and painstaking process. Dietary factors and related metabolic interactions have direct and indirect nutrient influence on specific gene regulation and expression. Research suggests that significant regulation appears to be at the level of transcription, with controlled modulation of messenger RNA levels. Data also indicate that nutritional factors, e.g., various vitamins regulated through dietary intake, can interact with other regulatory networks— such as tissue-specific, developmental, and hormonal factors, as well as dietary fat or carbohydrate—to regulate gene expression. Other studies have demonstrated regulation of apoprotein gene expression by sucrose-rich diet, nutritional regulation of gene expression in lipogenesis, and suppression of fatty acid synthase transcription by PUFA. Sanderson suggests that changes in the intestinal lumen can alter the expression of molecules in the intestinal epithelium that direct the mucosal immune system, with the intestinal epithelium acting as a relay for transducing the information of the intestinal environment to the mucosal immune system. Data indicate that this mechanism has advantages over other forms of immune surveillance in the gut that require the breach of invading organisms. Such breaches can be manipulated by invading organisms such as the polio virus to enter the body. Sanderson et al. suggest that other mechanisms (e.g., enteral feeds used to treat Crohn’s disease in children in the UK) can also alter the luminal environment radically enough to vary the signals from the intestinal epithelium to the mucosal immune system. Girard reports that until recently, the regulation of gene expression in response to changes in nutritional environment was thought to be mediated primarily by hormones and/or the nervous system. However, the last decade has provided evidence that major (glucose, fatty acids, amino acids) or minor (e.g., iron, vitamin) nutrients, or their respective metabolites, regulate gene expression in a hormone-independent manner. Recent experiments indicate that regulation of gene transcription is not a simple PPAR-mediated process. Rather, data show that a great diversity of fatty acid-sensor proteins and potential transcription factors are involved in fatty acid mediated gene expression. Sensors are known to relay the transcriptional effects of fatty acids, mediating them either directly, through their specific binding to various nuclear receptors (PPAR, LXR, HFN-4alpha), or indirectly, via modulations in the abundance of regulatory transcription factors (e.g., SREBP1-c, ChREBP). Each transcription factor makes a relative contribution to fatty acid-induced positive or negative gene expression. Fatty acids control the expression genes encoding regulatory protein involved in their own metabolism via molecular mechanisms. Nonesterified fatty acids or their CoA derivatives seem to be the main signals involved in the transcriptional effect of long-chain fatty acids. Growing knowledge of the mechanisms by which fatty acids control specific gene expression may provide insight into the development of new therapeutic strategies for better management of whole body lipid metabolism and the control of blood levels of triglycerides and cholesterol, major risk factors for coronary heart disease. Salati notes that regulation of the activity of enzymes involved in lipogenesis is key to understanding how a cell 1 Presented at the 6th Postgraduate Course on Nutrition entitled “Nutrition and Gene Regulation” Symposium at Harvard Medical School, Boston, MA, March 13–14, 2003. This symposium was supported by Conrad Taff Nutrition Educational Fund, ConAgra Foods, GlaxoSmithKline Consumer Healthcare, McNeil Nutritionals, Nestle Nutrition Institute, The Peanut Institute, Procter & Gamble Company Nutrition Science Institute, Ross Products Division–Abbott Laboratories, and Slim Fast Foods Company. The proceedings of this symposium are published as a supplement to The Journal of Nutrition. Guest editors for the supplement publication were: W. Allan Walker, Harvard Medical School, George Blackburn, Harvard Medical School, Edward Giovanucci, Harvard School of Public Health, Boston, MA, and Ian Sanderson, University of London, London, UK. 2 To whom correspondence should be addressed. E-mail: gblackbu@bidmc.harvard. edu.