Obesity, Nutrition and Nutri-genonmics Course lecturer : Jasmin Šutković 11th December 2015

Objectives Be familiar with the evidence for genetic influences on obesity Be able to define nutrigenomics Understand current limitations of nutrigenomic testing

Outline Background Genetics of Obesity Animals Humans Environmental effects Nutrigenomics Why the interest? Current products and examples Why the concern? Moving from promise to practice 5. Summary and Conclusions

Public Health Importance Mortality Increased risk of premature death Morbidity Diabetes, Heart disease, Hypertension, some Cancers, Breathing Problems, Ischemic Stroke, Arthritis, and Reproductive Complications Prevalence 59 million (30%) Americans are obese (BMI>= 30) Rates are increasing faster than ever (epidemic proportions)

Risk Factors for Obesity Diet: high calorie and low nutrient dense foods Physical Inactivity Age Socioeconomic status Certain medical conditions and medications Race Smoking cessation Family History Genetic susceptibility

Evidence for Genetic Influences on Obesity

Evidence for genetic influences: Humans Familial aggregation - familial clustering of obesity in families Twin Studies - greater concordance among MZ twins compared to DZ twins Family Studies - variety of “statistical models” consistent with genetic influences

The Search for Obesity Susceptibility Genes “I found one! I found one!” Kenneth M. Weiss & Joseph D. Terwilliger nature genetics • volume 26 • October 2000

Candidate Genes and Single Gene Disorders: Chromosomal Location Image adapted from: Loos, R. J. and C. Bouchard (2003). J Intern Med 254(5): 401-25.

Genetics of Human Obesity Common form(s) of obesity are likely due to complex interactions between genes and environment - body fat pattern - appetite regulation - other pathways Rare monogenic forms do not account for majority of cases

Nutrigenomics Integrates genomics and nutrition Goal: Improving health and preventing disease through tailored diet and lifestyle prescriptions

Nutrigenomics: Magic, Myths and Maybe’s

Nutrigenomics vs.Nutrigenetics “Nutrigenomics refers to the application of genomics in nutrition research, enabling associations to be made between specific nutrients and genetic factors, e.g. the way in which food or food ingredients influence gene expression… Nutrigenomics should facilitate greater understanding of how nutrition affects metabolic pathways and how this process goes awry in diet-related diseases.” Chadwick R. (2004) Proceedings of the Nutrition Society 63:161-166. Nutrigenetics “Nutrigenetics is the study of individual differences at the genetic level influencing response to diet. These individual differences may be at the level of single nucleotide polymorphisms rather than at the gene level…It is envisaged that nutrigenetics may lead to individualized dietary advice.” Chadwick R. (2004) Proceedings of the Nutrition Society 63:161-166.

Nutrigenomics & Nutrigenetics: Two Sides of a Coin

Nutritional Genomics The study of how different foods can interact with particular genes to increase the risk of diseases such as type 2 diabetes, obesity, heart disease and some cancers Goal: Use of personalized diets to prevent or delay the onset of disease and optimize and maintain human health http://nutrigenomics.ucdavis.edu/pressarticles.htm

Nutritional Genomics van Ommen B. (2004) Nutrition 20:4-8.

Why the interest? Improve health of populations Globally Improve athletic performance Weight loss Potential economic impact Functional food and dietary supplements is currently a $40 billion industry The focus on nutrigenomics could mean an $80 billion dollar industry in 7-10 years

What is the evidence? Single Gene Disorders Lactose intolerance Complex conditions Genes involved in susceptibility to complex diseases have been identified Nutritional environment modifies the expression of genes Metabolism of nutrients may vary by genotype, ultimately affecting health Singel gene disorders, good evidence for effective nutrition intervention based on genotype Complex conditions – although the evidence is increasing, evidence is less clear cut, -- efficacy has not been established and there will be challenges to doing this gene x e is difficult Large samples replicaiton

What is the public health implication? Can we use this information along with our increasing knowledge of the genetics of obesity for public health applications? Obesity epidemic Singel gene disorders, good evidence for effective nutrition intervention based on genotype Complex conditions – although the evidence is increasing, evidence is less clear cut, -- efficacy has not been established and there will be challenges to doing this gene x e is difficult Large samples replicaiton

Heart Health “Analyzes thirteen of your genes that may play an important role in determining how your body manages overall heart health” “…assesses nine key diet and lifestyle action areas”

Bone Health “Analyzes four of your genes that may play an important role in determining how your body manages overall bone health “..assesses seven key diet and lifestyle action areas”

Insulin Resistance “Analyzes five of your genes that may play an important role in determining how your body manages overall insulin resistance” “..assesses five key diet and lifestyle action areas”

Genetic Assessment for Antioxidant and Detoxification “Analyzes six of your genes that may play an important role in determining how your body manages overall antioxidant/ detoxification health” “..assesses four key diet and lifestyle action areas”

Inflammation Health “Analyzes six of your genes that may play an important role in determining how your body manages inflammation” “..assesses four key diet and lifestyle action areas”