20130919 Jornada Nutrición JM Ordovás: Nutrigenómica, hacia la nutrición personalizada

5. • Vitamin D Insufficiency
Linked to Adverse
Pregnancy Outcomes
• Chocolate consumption
may be linked to
Parkinson’s Disease
• Eating Eggs Raises Your
Cholesterol Level
• No Benefit Seen in
Sharp Limits on Salt in
Diet
• Too Much Vitamin D
During Pregnancy Can
Cause Food Allergies
• Dark Chocolate and
Red Wine the Food of
Love and Health
• Egg White Protein
May Help High Blood
Pressure
• Salt Levels in Food Still
Dangerously High

7. ¿

8. ¿

16. 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 1 2 3 4 5 6 7 8
hours
Postprandial Fasting

17. 50
70
90
110
130
150
170
190
0 1 2 3 4 5 6 7 8 9 10 11 12
TG(mg/dL)
hours after fat load
Boudewijn Klop, et al. Clinica Chimica Acta, 412:2183-2189 (2011)
D. Delawi et al. Clinica Chimica Acta, 328:139-145 (2003)
Men
Women
FCH
Normal

18. • Endothelial dysfunction
• Oxidant stress
• Hypercoagulability
• Sympathetic hyperactivity
• Triggering of acute inflammation
• Post meal increases in triglycerides, VLDL
remnants, HDL clearance and production of small
dense LDL particles

19. Aim
V0 -> Screening test
V1 -> Baseline Phenotypes
V2(0hr) -> Postprandial lipemia (PPL)
V2(3.5hr)
V2(6.5hr)
3-4 Weeks fenofibrate (160 mg)
V3 -> Postfenofibrate
V4(0hr) -> Postfenofibrate PPL
V4(3.5hr)
V4(6.5hr)
50
70
90
110
130
150
170
190
0 1 2 3 4 5 6 7 8 9 10 11 12
hoursafter fat load
TG(mg/dL)
50
70
90
110
130
150
170
190
0 1 2 3 4 5 6 7 8 9 10 11 12
hoursafter fat load
TG(mg/dL)
The postprandial fat-load test
consisted of a meal containing 700
cal/m2 body surface area; 3% of
cal. were derived from protein, 14%
from carbohydrate, and 83% from
fat sources. Cholesterol content was
240 mg and the ratio of PUFA to
SAT was 0.06. Participants were
instructed to consume this high-fat
meal within 15 min.

20. The gene-disease association network was created using
information from the Genetic Association Database of NIH
(http://geneticassociationdb.nih.gov), which is an archive of
human genetic association studies of complex diseases and
disorders. The network is made visual using Cytoscape software
(http://cytoscape.org). The blue hexagon represents disease,
the orange circles represent genes, and the width of the edges
represents the strength of association in the network.

21. before fenofibrate intervention
0
50
100
150
200
250
300
350
400
0,0 3,5 6,5
TG(mg/dl)
Hours
CG+GG
CC
after fenofibrate intervention
0
50
100
150
200
250
300
350
400
0,0 3,5 6,5
TG(mg/dl)
Hours
CG+GG
CC
P=0.003 P=0.129
CG+GG impaired metabolic
flexibility = higher CVD risk
CG+GG metabolic flexibility
“restored” with fenofibrate
Lai CQ et al. Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1417-25

22. 0,8
0,9
1
1,1
1,2
1,3
LOW HIGH
ORDiabetes
Adherence to the Mediterranean Diet
TT
TA+AA
Pint=0.036
Ortega-Azorín C, et al.. Cardiovasc Diabetol. 2012 Nov 6;11:137

23. Corella D, Carrasco P, Sorlí JV, Coltell O, Ortega-Azorín C, Guillén M, González JI, Sáiz C, Estruch R, Ordovas JM. Nutr
Metab Cardiovasc Dis. 2010 Dec 24.
(n=1580)
P interaccion FTO x Educacion = 0.048

24. 0
0,5
1
1,5
2
2,5
3
3,5
Control Mediterranean
HRSTROKE
DIET
CC
CT
TT
Cumulative stroke free-survival
by TCF7L2-rs7903146
genotypes in the control group
(A) (n = 2,291) and in the
MedDiet intervention groups
(B) (n = 4,827).
Corella D. et al. . Diabetes Care.
2013 Aug 13. [Epub ahead of
print] PubMed PMID: 23942586.

26. Genes tradicionales
x
Ambiente Moderno
=
Obesidad

27. • APOA2 -265T/C
• TT+TC 1994 cal/d88 kg
• CC 2200 cal/d92 kg
25
26
27
28
29
30
TT+TC CC
LSFD
HSFD
Pi=0.013 FHS
FHS
27
28
29
30
31
32
TT+TC CC
LSFD
HSFD
GOLDN
26
28
30
32
34
36
TT+TC CC
LSFD
HSFD
Pi=0.002 BPRHS
BPR
Smith CE et al. Int J Obes. 2012;36:130-6. Corella D et al. Int J Obes.
2011;35:666-75. Corella D et al. Arch Intern Med. 2009;169:1897-906. Corella D
et al. Clin Chem. 2007;53:1144-52.
Pi=0.009 GOLDN

28. Corella D, et al.. Arch Intern Med. 2009;169(20):1897-906.

30. Could out-of-sync body clocks be contributing to impaired phenotypic flexibility?

31. CONSEQUENCES
Obesity
Metabolic Syndrome
Cancer
Cardiovascular Disease
Mood Swings
Cognitive Problems
-Impaired synchronization
(continuous or intermittent light)
-Interfering with synchronicity
(eating late at night)
--Variable synchronicity (shift work)
-Variations in Clock Genes
(Clock, Bmal1, Per2)
-Oscillations external to the
superchiasmatic nucleus
- Melatonin
- Cortisol
Causes
Input
Clock
Output
Garaulet M and Madrid JA. International Journal of Obesity, 2009

33. 1900
1950
2000
2050
2100
2150
2200
2250
CC CT+TT
Calories/day
98.5
99
99.5
100
100.5
101
101.5
102
102.5
103
103.5
CC CT+TT
Waist Circumf.
Garaulet M, et al. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme
based on the Mediterranean diet. Int J Obes. 2010;34:516-23.
rs3749474 GENOTYPE

34. Garaulet M, et al. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme
based on the Mediterranean diet. Int J Obes. 2010;34:516-23.
1495 overweight/obese subjects (BMI:
25-40 kg/m2) of 20–65 y attending
outpatient obesity clinics
Dietary energy content
ranged from 1200–1800 kcal per day
for women and 1500-2000 kcal per
day for men to induce an
approximate loss of
0.5–1 kg per week.
The recommendations were consistent
with the Mediterranean type of diet
CC+TC
TT
Minor C allele carriers had:
• shorter sleep duration
• higher plasma ghrelin concentrations
• delayed breakfast time
• evening preference
• less compliance with a Med Diet pattern
0%
20%
40%
60%
80%
100%
European Asian African Native
Americans
T
C

36. Dejo mis bienes a mi sobrino Juan no a mi hermano Luis tampoco jamás páguese la cuenta al sastre nunca
de ningún modo para los jesuitas todo lo dicho es mi deseo.
Mucha atención:
Juan dirá que: Dejo mis bienes a mi sobrino Juan, no a mi hermano Luis. Tampoco, jamás, páguese la cuenta
al sastre. Nunca, de ningún modo para los jesuitas. Todo lo dicho es mi deseo. Y así la fortuna es de Juan.
Luis dirá: ¿Dejo mis bienes a mi sobrino Juan? No, a mi hermano Luis. Tampoco, jamás, páguese la cuenta al
sastre. Nunca, de ningún modo para los jesuitas. Todo lo dicho es mi deseo. Gana Luis.
El sastre dice lo contrario: ¿Dejo mis bienes a mi sobrino Juan? No ¿A mi hermano Luis? Tampoco, jamás.
Páguese la cuenta al sastre. Nunca, de ningún modo para los jesuitas. Todo lo dicho es mi deseo. El sastre se
va con platita.
Los jesuitas, con el favor de Dios, dirán: ¿Dejo mis bienes a mi sobrino Juan? No ¿A mi hermano Luis?
Tampoco. Jamás páguese la cuenta al sastre, nunca, de ningún modo. Para los jesuitas. Todo lo dicho es mi
deseo.
Como no se ponían nunca de acuerdo, llego el estado y dijo -Todos quieren cometer fraude, esto es
así: ¿Dejo mis bienes a mi sobrino Juan? No ¿A mi hermano Luis? Tampoco. Jamás páguese la cuenta al
sastre, nunca. De ningún modo para los jesuitas. Todo lo dicho es mi deseo. Por lo que el dinero es para el
estado, ya que no hay herederos.

37. Epigenetic Gene Promoter Methylation at
Birth Is Associated With Child’s Later
Adiposity
9 years later
Godfrey KM, et al. Diabetes. 2011 May;60(5):1528-34

38. RNA-induced
silencing complex

39. 90% of cells in the human body are bacterial,
fungal, or otherwise non-human.
There are millions of genes in our “extended
genome” compared to the nearly 23,000 in
the human genome

41. Azad MB, Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013 Feb 11. Ottman N,
Smidt H, de Vos WM, Belzer C. The function of our microbiota: who is out there and what do they do? Front Cell Infect Microbiol. 2012;2:104.

43. 48
6842
Ejercicio
Hipocalorica
HC Complejos
Grasas
Tratamiento estándar
Tratamiento Individualizado
(genético)
PPARα 162V+ 2
LPL S447X + 1
8
42
38
12
Ejercicio
Hipocalorica
HC Complejos
Grasas
PLIN 11482 G>A + 4
ACSL5 + 3
Tratamiento Estándar
personalizado
(genética)
Ejercicio 25% 8%
Hipocalórica 25% 42%
HC Complejos 25% 38%
Grasas 25% 12%
Total 100% 100%
Tratamiento Estándar
personalizado
(genético)
Ejercicio 25% 48%
Hipocalórica 25% 6%
HC Complejos 25% 8%
Grasas 25% 42%
Total 100% 100%
Subject 1 Subject 2

47. Preventive
Participatory
Pleasurable