Lecture 4: Nutrition, Nutrigenomics, Nutrigenetics

• Nutrigenomics


  The nutrition interacts with the genome
• Nutrition has an important chronic impact on human health
• Nutrigenetics


  The influence of the genetic layout on the response to a diet
• Nutrigenomics


  The influence of nutrients, or the diet on gene regulation
• Nutrigenetics example: Lactose Intolerance


  • Lactose cannot be utilised because of the genetic composition
  • Mutations in lactase genes lead to lactose intolerance
  • Lactose → Lactase (hydrolysis)→ Galactose and Glucose : No lactase means lactose can not break down and it will accumulate → lead to osmotic imbalance
• Originally adult humans were lactose intolerant

  Domestication of cattle reintroduced lactose tolerance
• Selection Advantage


  Prevalence of Lactose Intolerance in Adults → Higher in countries where cattles were domesticated for longer (e.g. Europe and Asia)
• Nutrigenomics influences gene regulation at four levels

  • Genomics → Sequencing and Genotyping
  • Transcriptomics → Patterns of gene expression
  • Proteomics → Synthesis and Structures of Proteins
  • Metabolomics → Profile and function of metabolites
• Chronic caloric restriction increases life expectancy in mammals
• Chronic Caloric Restriction (30%) reduces the incidence of age related diseases in Rhesus Monkeys (Neoplasia, CVD, Glucoregulatory impairment)
• Sirtuins


  Important targets in ageing research
• Knockout of SIRT1 in mice inhibits the effect of caloric restriction on ageing
• Caloric restriction increases SIRT1-expression in mice and humans
• Deacetylation of proteins by sirtuins

  Acetylated proteins → Sirtuin (NAD+ → NAM → NAMPT) → De-acetylated proteins (2'-O-Acetyl-ADP Ribose) + protein + Ac groups
• Sirtuins

  • Act on: Senescence, survival, DNA repair, Metabolism, Proliferation
• Decrease NAD+/NADH (Nutrients high)


  Increase Sirtuin activity to Increase NAD+/NADH (Nutrients low)
• Compounds that increase Sirtuin expression W/OUT CALORIC RESTRICTION

  • Resveratrol from red wine
  • Butein
• Resveratrol increases lifespan of several model organisms (and decrease bw)
• Resveratrol and caloric restriction have similar effects on lifespan
• Consuming a high-fat diet rich in saturated fats can exacerbate hypothalamic inflammatory response
• Unsaturated fatty acids act on neurons to counteract the inflammatory effects caused by saturated fatty acids
• Hypothalamic inflammation pathway


  Saturated fats bind to TLR4 ligand receptor → IKKB → NF-kB (=p65, IxBa, p50) activation → Gene transcription leading to Cytokine release, Inhibition Insulin/Leptin → Diabetes II?
• Blocking hypothalamic inflammation protects from obesity
• Studies on ...

  • Study 1: Butein (plant polyphenols)effectively lowers glucose levels by inhibiting NF-kB and NF-kB-regulated gene expression

  • Study 2: Addition of gluten to high fat diet increases body weight in mice