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We are what we eat
The path from public health to personal health
                 Michael Müller
                    Netherlands Nutrigenomics Centre
               & Nutrition, Metabolism and Genomics Group
           Division of Human Nutrition, Wageningen University
Human Nutrition: State-of-the-art ?




                                1883
I have a dream
“I track, therefore I am”
2013 – our health (care) reality
•   The next health tsunami => non-communicable diseases (NCDs) >
    communicable diseases (CDs).
•   Our research is often still focused on treatment instead of prevention of NCDs.
•   Research is largely fragmented with the ambition to find “magic bullets”: gene X
    is responsible for the disease & could be drug target.
•   We have no efficient strategies to treat or cure complex NCDs (Diabetes, CVD,
    cancer, mental disorders) => chronic diseases that require life-long treatment.
•   Mono-target approaches (“one drug fits all” bestsellers) fail in the efficient
    treatment of NCD => increasing health care costs & decreasing quality of life.
•   A “creative deconstruction of medicine (Eric Topol) and health care” is needed.



               We need a new dynamic health concept based
                  on metabolic plasticity and resilience =>
               “Health as the capacity to adapt to challenges!”
Nutrigenomics & molecular nutrition allows
 us to define the mechanistic framework




                                   Blood
                                   triglycerides
“2 hits” in Metabolic Syndrome
  “Too much metabolic & inflammatory stress”
Complex NC diseases are caused by dysregulation




                Nature Medicine 2012
Energy homeostasis & obesity
Genes and Nutrition => Phenotype
       Its not that easy
Classification of hereditary diseases
SNP-trait associations
detected in GWA studies
Understanding Nutrition
        How nutrients regulate our genes: via sensing molecular switches



                                                                                                                                                       Changed
                                                                                                                                                        organ
                                                                                                                                                       metabolic
                                                                                                                                                       capacity




J Clin Invest. 2004;114:94-103                  BMC Genomics 2008; 9:262                     Physiol. Genomics 2009                   PLoS One. 2012;7(8):e43260.
J Biol Chem. 2006;28:934-44                     J Biol Chem. 2008;283:22620-7                Circulation 2010                         J Hepatol. 2012 Dec;57(6):1370-3.
Endocrinology. 2006;147:1508-16                 Arterioscler Thromb Vasc Biol. 2009;29:969-74.
                                                                                             Diabetes 2010                            Am J Physiol Gastrointest Liver Physiol. 2012
Physiol Genomics. 2007;30:192-204               Plos One 2009;4(8):e6796                     Cell Metabolism 2010                     Physiol Genomics. 2012 Mar 19;44(6):352-61.
Endocrinology. 2007;148:2753-63                 Hepatology 2010;51:511-522                   Physiol Genomics. 2011;43(23):1307-18.   Am J Physiol Endocrinol Metab. 2012
BMC Genomics 2007; 8:267                        Am J Clin Nutr. 2009; 90:415-24              PLoS One. 2011;6(4):e19145.              Prog Lipid Res. 2012 Jan;51(1):63-70.
Arterioscler Thromb Vasc Biol. 2007;27:2420-7   Am J Clin Nutr. 2009;90:1656-64              Nature 2011 May 22                       Mol Cell Biol. 2013 Jan 22.
Am J Clin Nutr. 2007;86(5):1515-23              Mol Cell Biology 2009;29:6257-67             PLoS One. 2012;7(12):e49868.             Hepatology. 2013 Jan 21.
PLOS ONE 2008;3(2):e1681                        Am J Clin Nutr. 2010;91:208-17               PLoS One. 2012;7(11):e51066.             J Nutr. 2013 Jan 16.
BMC Genomics 2008; 9:231                        BMC Genomics 2009                            PLoS One. 2012;7(10):e47303.             Carcinogenesis. 2013 March
                                                                                             BMC Med Genomics. 2012 Aug 28
Phenotype plasticity
Phenotypic plasticity is the ability of an organism to
change its phenotype in response to changes in the
environment (e.g. nutrition or exercise).




                                                                                                     CYP4A10

                                                     14

                                                     12

                                                     10




                                     FC vs WT ctrl
                                                      8

                                                      6

                                                      4

                                                      2

                                                      0
                                                          WT          KO   WT    KO   WT   KO   WT   KO   WT   KO   WT   KO   WT   KO   WT   KO   WT   KO

                                                               ctrl         WY         feno     C10:0TG   C18:1TG   C18:2TG   C18:3TG   C20:5TG   C22:6TG
Your are what you eat
  Healthy food (pattern)s have large impact on our gene expression & phenotype



• (Micro & Macro) Nutrients
   – Mono & polyunsaturated fatty acids
   – Vitamines (e.g. vitamine A & D) , minerals (e.g. Zn)
• Microbiota (from foods)
   – Vegetarians / omni- /carnivores => different microbiota
   – “Raw” (e.g. “Sushi”) or fermented food consumption => food-
     specific microbiota
• Food components (bitter, toxic, “healthy”)
   – Secondary plant metabolites (e.g. resveratrol, glucosinolates,
     cafestol....)
   – MicroRNA (e.g. rice) => “nutrient”?
• Less foods/calories (caloric restriction) => “chromatin”
  exercise
We are what we eat - a path towards personal health
“We are what we eat and have eaten”
Received, Recorded, Remembered & Revealed
Nutrigenomics
Quantification of the nutritional genotype-phenotype

                      Phenotype




                      Metabolome
  Lifestyle
                       Proteome
 Nutrition
 Microbiota
                     Transcriptome
Environment
                      Epigenome


                       Genotype
chronically
            Examples: Do not overload organs
                                  40 cm
4 cm




C1     C2     C3      C4     C5      C6     C7   C8   C9   C10




       10% FAT

                   45% FAT
„Obese-linked‟ pro-inflammatory
  gene expression profile by SFAs
SFA diet   MUFA diet
                       • The SFA-rich diet:
                       • Induces a pro-
                         inflammatory obese-linked
                         gene expression profile

                       • Decreases expression and
                         plasma level of the anti-
                         inflammatory cytokine
                         adiponectin

                       • “Personal Transcriptomes”
                           Van Dijk et al. AJCN 2009
How to age successfully?
Its easy (if your genes are ok)
2 Meals a day, work as long as possible & embrace
                    challenges




              Walter Breuning (1896 - 2011)
Finally
         “You are what you eat”
Enjoy the huge diversity of food patterns

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We are what we eat - a path towards personal health

  • 1. We are what we eat The path from public health to personal health Michael Müller Netherlands Nutrigenomics Centre & Nutrition, Metabolism and Genomics Group Division of Human Nutrition, Wageningen University
  • 3. I have a dream “I track, therefore I am”
  • 4. 2013 – our health (care) reality • The next health tsunami => non-communicable diseases (NCDs) > communicable diseases (CDs). • Our research is often still focused on treatment instead of prevention of NCDs. • Research is largely fragmented with the ambition to find “magic bullets”: gene X is responsible for the disease & could be drug target. • We have no efficient strategies to treat or cure complex NCDs (Diabetes, CVD, cancer, mental disorders) => chronic diseases that require life-long treatment. • Mono-target approaches (“one drug fits all” bestsellers) fail in the efficient treatment of NCD => increasing health care costs & decreasing quality of life. • A “creative deconstruction of medicine (Eric Topol) and health care” is needed. We need a new dynamic health concept based on metabolic plasticity and resilience => “Health as the capacity to adapt to challenges!”
  • 5. Nutrigenomics & molecular nutrition allows us to define the mechanistic framework Blood triglycerides
  • 6. “2 hits” in Metabolic Syndrome “Too much metabolic & inflammatory stress” Complex NC diseases are caused by dysregulation Nature Medicine 2012
  • 8. Genes and Nutrition => Phenotype Its not that easy
  • 11. Understanding Nutrition How nutrients regulate our genes: via sensing molecular switches Changed organ metabolic capacity J Clin Invest. 2004;114:94-103 BMC Genomics 2008; 9:262 Physiol. Genomics 2009 PLoS One. 2012;7(8):e43260. J Biol Chem. 2006;28:934-44 J Biol Chem. 2008;283:22620-7 Circulation 2010 J Hepatol. 2012 Dec;57(6):1370-3. Endocrinology. 2006;147:1508-16 Arterioscler Thromb Vasc Biol. 2009;29:969-74. Diabetes 2010 Am J Physiol Gastrointest Liver Physiol. 2012 Physiol Genomics. 2007;30:192-204 Plos One 2009;4(8):e6796 Cell Metabolism 2010 Physiol Genomics. 2012 Mar 19;44(6):352-61. Endocrinology. 2007;148:2753-63 Hepatology 2010;51:511-522 Physiol Genomics. 2011;43(23):1307-18. Am J Physiol Endocrinol Metab. 2012 BMC Genomics 2007; 8:267 Am J Clin Nutr. 2009; 90:415-24 PLoS One. 2011;6(4):e19145. Prog Lipid Res. 2012 Jan;51(1):63-70. Arterioscler Thromb Vasc Biol. 2007;27:2420-7 Am J Clin Nutr. 2009;90:1656-64 Nature 2011 May 22 Mol Cell Biol. 2013 Jan 22. Am J Clin Nutr. 2007;86(5):1515-23 Mol Cell Biology 2009;29:6257-67 PLoS One. 2012;7(12):e49868. Hepatology. 2013 Jan 21. PLOS ONE 2008;3(2):e1681 Am J Clin Nutr. 2010;91:208-17 PLoS One. 2012;7(11):e51066. J Nutr. 2013 Jan 16. BMC Genomics 2008; 9:231 BMC Genomics 2009 PLoS One. 2012;7(10):e47303. Carcinogenesis. 2013 March BMC Med Genomics. 2012 Aug 28
  • 12. Phenotype plasticity Phenotypic plasticity is the ability of an organism to change its phenotype in response to changes in the environment (e.g. nutrition or exercise). CYP4A10 14 12 10 FC vs WT ctrl 8 6 4 2 0 WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO ctrl WY feno C10:0TG C18:1TG C18:2TG C18:3TG C20:5TG C22:6TG
  • 13. Your are what you eat Healthy food (pattern)s have large impact on our gene expression & phenotype • (Micro & Macro) Nutrients – Mono & polyunsaturated fatty acids – Vitamines (e.g. vitamine A & D) , minerals (e.g. Zn) • Microbiota (from foods) – Vegetarians / omni- /carnivores => different microbiota – “Raw” (e.g. “Sushi”) or fermented food consumption => food- specific microbiota • Food components (bitter, toxic, “healthy”) – Secondary plant metabolites (e.g. resveratrol, glucosinolates, cafestol....) – MicroRNA (e.g. rice) => “nutrient”? • Less foods/calories (caloric restriction) => “chromatin” exercise
  • 15. “We are what we eat and have eaten” Received, Recorded, Remembered & Revealed
  • 16. Nutrigenomics Quantification of the nutritional genotype-phenotype Phenotype Metabolome Lifestyle Proteome Nutrition Microbiota Transcriptome Environment Epigenome Genotype
  • 17. chronically Examples: Do not overload organs 40 cm 4 cm C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 10% FAT 45% FAT
  • 18. „Obese-linked‟ pro-inflammatory gene expression profile by SFAs SFA diet MUFA diet • The SFA-rich diet: • Induces a pro- inflammatory obese-linked gene expression profile • Decreases expression and plasma level of the anti- inflammatory cytokine adiponectin • “Personal Transcriptomes” Van Dijk et al. AJCN 2009
  • 19. How to age successfully?
  • 20. Its easy (if your genes are ok) 2 Meals a day, work as long as possible & embrace challenges Walter Breuning (1896 - 2011)
  • 21. Finally “You are what you eat” Enjoy the huge diversity of food patterns