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

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• 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

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

0 1 2 3 4 5 6 7 8 9 10 11 12

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)

Normal

• 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

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)

0 1 2 3 4 5 6 7 8 9 10 11 12

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.

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.

before fenofibrate intervention

0,0 3,5 6,5

after fenofibrate intervention

0,0 3,5 6,5T

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

LOW HIGH

Adherence to the Mediterranean Diet

Pint=0.036

Ortega-Azorín C, et al.. Cardiovasc Diabetol. 2012 Nov 6;11:137

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

Control Mediterranean

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.

Genes tradicionales

Ambiente Moderno

Obesidad

• APOA2 -265T/C

• TT+TC 1994 cal/d88 kg

• CC 2200 cal/d92 kg

252627282930

TT+TC CC

Pi=0.013 FHS FHS

272829303132

TT+TC CC

Pi=0.002 BPRHS

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

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

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

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

Output

Garaulet M and Madrid JA. International Journal of Obesity, 2009

CC CT+TT

Calories/day

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

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

Minor C allele carriers had:

• shorter sleep duration

• higher plasma ghrelin concentrations

• delayed breakfast time

• evening preference

• less compliance with a Med Diet pattern

European Asian African NativeAmericans

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.

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

RNA-induced silencing complex

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

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.

6 8 42

Ejercicio

Hipocalorica

HC Complejos

Grasas

Tratamiento estándar

Tratamiento Individualizado(genético)

PPARα 162V+ 2

LPL S447X + 1

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

Preventive

Participatory

Pleasurable

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

Health & Medicine