Nutrigenomik :

Era Baru Studi Gizi dan Kesehatan

Rimbawan
Dept Gizi Masyarakat
Institut Pertanian Bogor
Pendahuluan

Hippocrates (2500 years ago):

 You are what you
eat
Ludwig Feuerbach

Tell me what you eat,

I will tell you what you are
• The interaction between the human body
and nutrition is an extremely complex
process involving multi-organ physiology
with molecular mechanisms on all levels
of regulation (genes, gene expression,
proteins, metabolites).
• Only with the recent technology push
have nutritional scientists been able to
address this complexity.
• Nutrients have long been considered merely as fuel or
cofactors. They can themselves participate in the
regulation of metabolic pathways, for instance through
the allosteric regulation of specific enzymes, or by
modulating hormone secretion.
• When molecular biology reached laboratories dealing
with the physiology of nutrition and metabolism, it was
realized that nutrients either directly or through their
hormonal consequences were able to strongly modify
the expression of genes (and thus of proteins).
• Also, the influence of variations in the genome on
nutrient utilization and diet-dependent health status
(obesity, type 2 diabetes, cancer, cardiovascular
diseases) was demonstrated.
Kaput, (2007). Bruce Ames Int. Symp. Nutr. Genomics, USA
 Do nutrients affect gene expression?

 Vitamin E regulates protein kinase C activity in smooth muscle

cells (Azzi 1991)
 Modulates the expression of the hepatic alpha-tocopherol
transfer protein (Hosomi 1997)
 Tocopherol-dependent transcription factor (tocopherol
associated protein, TAP) has been identified (Stocker 1999)
 CoQ10 in human muscle cells has shown effects on 12,000
genes (Linnane 2002)
 Vitamin D3 affects 20,000 genes in human prostate cancer cells
(Krishnan 2003)
 FOOD

Kaput, (2007). Bruce Ames Int. Symp. Nutr. Genomics, USA

 Nutrigenetics
 SNPs occur once every 1k to 2k
• Nutrigenetics nucleotides, but occur at a
frequency > 1% in the population
– Nutrition + genetics  Effects can be variable and not
– How does individual always dramatic
 Can alter protein structure
genetic variability and function when the
shape nutrient nucleotide base substitution
metabolism? occurs in a gene’s coding
region
– Can this help shape  When substitution occurs as
individual nutrient part of the gene’s regulatory
promoter, the SNP may
requirements for affect the conditions under
health and optimized which the protein is made
performance?

Wood and Bakovic, 2007

The difference is not in the sequence of the
genetic code

The difference is how the sequence of the genetic

code is regulated
 Dietary Chemicals and Gene
Expression

• Epidemiological studies repeatedly show

associations between food intake and the
incidence and severity of chronic
diseases.
• Common dietary chemicals act on the
human genome directly or indirectly to
alter gene expression or structure.

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Interaction of nutrients and gene
expression
A) Direct - Nutrients act as
ligands for transcription factor
receptors.
B) Indirect – Nutrients are
metabolized by primary or
secondary metabolic
pathways, altering
concentrations of substrates
or intermediates.
C) Indirect – Nutrients alter signal
transduction pathways and
signaling
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14% of Utah families with positive history of
CHD account for
•72% of all premature (<50 Yrs) CHD events
•48% of all CHD events

11% of Utah families with a positive family

history of stroke account for
•86% of all strokes
Hunt et al (2003), Am J Prev Med. 24, 136