1) Replacing carbohydrates with proteins in a low-calorie diet promotes weight and fat loss (10% and 5.5% respectively), and increases the endogenous oxidation of lipids without affecting protein metabolism. 2) Lipid utilization after consuming a high-protein meal is significantly higher compared to a high-carbohydrate meal. 3) Increasing protein content at the expense of carbohydrates in a low-calorie diet specifically increases mitochondrial oxidation, limiting the decrease in resting energy expenditure compared to caloric restriction.

1. J. Alfredo Martínez Hernández
Granada 18th sept 2013
Benefits and mechanisms of moderately high protein or
high fiber diets in body weight loss and maintenance:
The DIOGENES project
Departamento de Nutrición, Ciencias de la
Alimentación y Fisiología
Pamplona
Spain

3. INTRODUCCIÓN

4. High Prevalence
Public health Burden
Mortality cause
Hypertension, hiperinsulinemia, dislipidemias,
diabetes, cardiovascular diseases and cáncer
OBESITY PREVALENCE
Life quality impairments
Introducción
SPAIN
33%
11%
PORTUGAL
33%
9%
FRANCE
24%
7%
IRELAND
31%
8%
NETHERLANDS
29%
10%
U. K.
30%
12%
BELGIUM
31%
9%
DENMARK
31%
8%
SWEDEN
33%
7%
LUXEMBOURG
27%
9%
ITALY
30%
7% GREECE
35%
11%
GERMANY
35%
11%
AUSTRIA
32%
10%
FINLAND
33%
10%
33% OW

5. Genetics
Introducción
BODY FAT
EXCESS
OBESITY
DEFINICIÓN DE OBESIDAD
Environment
Lifestyle
+
+ +
ENERGY
INTAKE
ENERGY
EXPENDITURE
Neuroendocrine
factors
- -

6. ADIPOSITY
Fatty acids
Metabolic Syndrome
Glucose Intolerance
Diabetes mellitus type II
Inflammation
Hypertension
Glucose
intolerance
Atherosclerosis
Insulin
Resistance
Endothelial
dysfunctions
Introducción

7. TRATAMIENTO DE LA OBESIDAD
Negative Energy
Balance
Weight and fat loss
RISK FACTORS IMPROVEMENT
Objetive
intake
Energy expenditure
Introducción

8. OBESITY TREATMENT
Nutritional therapies Lifestyle Adaptation
Physical Activity
programmes
Pharmacological approaches
Surgery
1º
2º
3º
Introducción

9. DIETS
Low Carb vs High
protein diets
High carb / low fat diets
GI
VLCD 400-1000 kcal
Products,………
Capsules, powders, teas…
Specific foods
Pinaapple,
cider,apple,berries,..…

10. Macronutrient distribution may
have a role in body weight loss and
maintenance as well as on
associated obesity manifestations
Hipótesis

11. LOW CALORIE DIETS
Fat losses
lean tissue maintenance
Macronutrient distribution
Food Composition
Proteins, 3 fatty acids,
glycemic index, fiber,
amino acids…
Risk factors
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 2
Carbohydrates
Lípids
Proteíns

12. Body weight composition
DEXA, Bio-impedance
Energy expenditure
Indirect Calorimetry
Mitochondrial Oxidation
Breath tests for stable isotopes
Blood Sampling
Lipids, carbohydrates, leptin Energy
expenditure
Energy - 30%
DIET
Anthropometrics
Weight, stature, circumferences,……..
Material y Métodos

13. RESULTADOS:

14. Resultados

15. Labayen et al. 2004,Clin Nutr; 23:571-578
Net Lipid Oxidation
Resultados

16. Resultados

17. Labayen et al. 2004,Nutr Res; 24: 7-18
Efecto termogénico y utilización postprandial de nutrientes
Fat Balance
-180
-160
-140
-120
-100
-80
-60
-40
-20
0
Day 0 Day 70
Fatbalance(kJ)
* P < 0.10
Resultados

18. EFECTS OF PROTEIN VS CARBOHYDRATE-RICH DIETS
ON FUEL UTILISATION IN OBESE WOMEN DURING
WEIGHT LOSS
Elmadfa I, Ankalm E, König JS (eds): Modern Aspects of Nutrition. Present knowledge
and future perspectives. Forum Nutr. Basel, Karger, 2003, vol 56: 168-170
Labayen I, Díez N, González A, Parra D, Martínez JA
Resultados

19. Labayen et al., 2003. Forum Nutr. 23: 168-170
Cambios en leptina y utilización de nutrientes
+51% (p<0.05) in leptin concentration in protein diet.
OXIDACIÓN DE PROTEÍNAS
0
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
2
Dieta HP Dieta HC
Tasadeoxidación(g/kg*d)
Inicio
Final
p=0.052
Resultados
HP Diet HC Diet
Basal
Final

20. Resultados

21. EFECTO SOBRE LA OXIDACIÓN MITOCONDRIAL:
Test en aliento 2-ceto[1-13C]isocaproato
25
27
29
31
33
35
37
Dieta control Dieta hiperproteíca
Inicio
Final
p=0.036
p=0.597
TrazerOxidation(%)
Abete et al., 2008. Int J Food Sci Nutr; 1-13
Resultados
Control diet High protein diet
Basal
Final

22. Resultados

23. N=10
CONTROL
N=9
HIGH PROTEIN
N=8
LEGUMES
N=8
FATTY FISH
35 Men; Age: 387 years;
BMI: 31,83,0 kg/m2
>Protein
<Carbohydrates
30%P; 33%CHO; 37%FAT
> Fiber
>Protein
19%P; 52%CHO; 30% FAT
> 3 Fatty acids
18.5%P; 51%CHO; 32%AG
Balanced Energy restricted
19%P; 51%CHO; 30%FAT
Resultados

24. Pérdida de peso durante el período de intervención nutricional
Abete et al., 2008. J Med Food; 12:100-108
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
0 1 2 3 4 5 6 7 8
Dieta control
Dieta legumbres
Dieta pescado azul
Dieta hiperproteica
Pérdidadepeso(%)
* *
#
Energy restriction effect p<0,001
Weeks
Dier effect p=0,05
# p<0,05 legumes vs control
* p<0,05 Higher protein vs control
Resultados
Control diet
Legumes diet
Fatty fish diet
High protein diet

25. Waist
Circumference
(%)
-14
-12
-10
-8
-6
-4
-2
0
Dieta control Dieta legumbres
Dieta pescado
azul Dieta hiperproteica
*
*
*
*
FatMass(%)
-25
-20
-15
-10
-5
0
Dieta control Dieta legumbres
Dieta pescado
azul Dieta hiperproteica
* * * *
-7,6
-7,55
-7,5
-7,45
-7,4
-7,35
-7,3
Dieta control Dieta legumbres
Dieta pescado
azul
Dieta
hiperproteica
Restingenergy
expenditure(%)
* * * *
Cambios observados tras el período de intervención nutricional
*P<0,05. Basal vs final Abete et al., 2008. J Med Food; 12:100-108
Resultados
Control diet
Legume
diet
Fatty fish
diet
High protein
diet Control diet
Legume
diet
Fatty fish
diet
High protein
diet
Control diet
Legume
diet
Fatty fish
diet
High protein
diet

26. Resultados

27. EVOLUCIÓN DE LA PERDIDA DE PESO

28. Resultados

29. Larsen et al, 2010. N Engl J Med; 363:2102-13
Background
PROYECTO DiOGenes: Diet, Obesity and Genes. 8 European countries
Nutritional Intervention
- PHASE I: Weight loss  - 800 kcal for 8 weeks
- PHASE II: Mantenimiento  Maintenance for 26 weeks .
1209 adults 938 PHASE I  773 adults in PHASE II
Resultados

30. Larsen et al, 2010. N Engl J Med; 363:2102-13
PHASE II: Weight Maintenance
773 adults with weight loss >8%
↑ Prot
↓ IG
Control↑ Prot
↑ IG
↓ Prot
↑ IG
↓ Prot
↓ IG
N= 159 N= 155 N= 150N= 154 N= 155
Protein = 25% E
GI= 58.0 vs 61.3
Protein = 13% E
IG = 58.2 vs 61.4
AD LIBITUM WITH NO ENERGY RESTRICTION !
 26 weeks with monthly advice.
Resultados

31. Larsen et al, 2010. N Engl J Med; 363:2102-13
CAMBIOS EN PESO CORPORAL
Resultados

32. Resultados

33. Resultados

35. Possible interactions of dietary intake with genetic variability to affect disease risk.
Jenab MZ et al. Hum Genet (2009) 125: 507–525
Nutrition and genetic interactions

36.  DEPARTAMENTO DE CIENCIAS DE LA ALIMENTACIÓN,
FISIOLOGÍA Y TOXICOLOGÍA
 GOBIERNO DE NAVARRA Y UNIÓN EUROPEA
Agradecimientos

38. Resultados

39. Resultados

40. Resultados

41. DNA RNA PROTEINS
Transcription Translation
Gene Expression= f (DNA  Environmental factors)
GENOTYPE  PHENOTYPE

42. Regulatory Elements Estructural Functions
Proteins
Energy
Nutrients
NUTRIENT FUNCTIONS

43. Fatty Acids
Retinoids
Vitamin D
Glucose
Energy
Transcription
mRNADNA Proteíns
Translation
Amino acids
Iron
Selenium
Postranslation
Minerals
Vitamins
Gene expression – Nutritional control

44. Cascade
Kinases
Mechanisms : - Receptors (membrane/nucleus)
Nutrients
Nutrients

Nutrients &
Metabolites
- Metabolism intermediate
FT
- Transcription Factors (FT): affinity & concentrations
RE
Gene expression control: Mechanisms

45. Genetic make up can determine
unique nutritional requirements
and responses to different foods.
Based on:
- The sequencing of the human genome,
- subsequent analyses of human genetic variation,
-studies that associate gene variants with disease markers
-Impact of nutrition/nutrients on gene expression
Personalized Medicine and Nutrition

53. Epigenetic processes modulate gene activity and expression
without changes in the DNA nucleotide sequence
EPIGENETICS

54. Me
DNA Methylation
Histone Modifications DNA Packaging
around Nucleosomes
Me
Me
Chromatin Packaging
Alterations
Me
Me
Me
Me
Me
Me
Me
Me
Me Me
Me MeAc Ac Ac
Ac
Epigenetic Modifications

56. Sullivan KE et al.
Epigenetic regulation of tumor necrosis factor alpha.
Mol Cell Biol 2007, 27: 5147-5160.
TNF-α promoter methylation is tissue
specific

57. 24 obese subjects
(BMI: 30.5 ± 1.5 kg/m2)
12 men 12 female
Serum: TNF-a
Blood, PBMC: DNA
8-week hypocaloric diet
Weigh loss ≥ 5% of initial body
Responders Non-responders
Serum: TNF-a
Experimental design

58. TNF-a gene
% Methylation

59. Weight Loss
Baseline TNF-a
Final TNF-a
Subjects less
methylated lose
more weight
Subjects with more
baseline TNF have
the promoter
more methylated
Subjects with the
promoter more
methylated decrease
less the TNF levels
Results

60. CONCLUSIONES

61. Conclusiones
2) La utilización de lípidos tras la ingesta de una comida con
alto aporte proteico es significativamente mayor
comparada con una comida alta en hidratos de carbono.
1) La sustitución de hidratos de carbono por proteínas en el
contexto de una dieta hipocalórica favorece la pérdida
de peso y masa grasa (10% y 5.5%, respectivamente),
además de promover la oxidación endógena de lípidos
sin afectar al metabolismo proteico.

62. 3) El aumento del contenido proteico a expensas de los
hidratos de carbono dentro de una dieta hipocalórica
produjo un aumento específico de la oxidación
mitocondrial, limitando el descenso del gasto energético
en reposo frente a la restricción calórica
4) Las dietas hiperproteicas pueden ser una estrategia
dietética a corto plazo más efectiva en cuanto a la
pérdida de peso, masa grasa, resistencia a la insulina,
control del apetito y descenso del gasto energético en
reposo.
Conclusiones

63. Conclusiones
5) La ingesta moderadamente alta de proteína y la
reducción del índice glucémico dentro de una dieta
habitual favorece el mantenimiento de peso, evitando la
recuperación del peso perdido y de la masa grasa
específicamente.

64. Genetics Genomics Epigenetics
Nutrition, perinatal programming and
disease

65. Nutrition and Health

66. Genetics Genomics Epigenetics
Nutrition, perinatal programming and
disease

74. CONCLUSIONES

75. Conclusiones
2) La utilización de lípidos tras la ingesta de una comida con
alto aporte proteico es significativamente mayor
comparada con una comida alta en hidratos de carbono.
1) La sustitución de hidratos de carbono por proteínas en el
contexto de una dieta hipocalórica favorece la pérdida
de peso y masa grasa (10% y 5.5%, respectivamente),
además de promover la oxidación endógena de lípidos
sin afectar al metabolismo proteico.

76. 3) El aumento del contenido proteico a expensas de los
hidratos de carbono dentro de una dieta hipocalórica
produjo un aumento específico de la oxidación
mitocondrial, limitando el descenso del gasto energético
en reposo frente a la restricción calórica
4) Las dietas hiperproteicas pueden ser una estrategia
dietética a corto plazo más efectiva en cuanto a la
pérdida de peso, masa grasa, resistencia a la insulina,
control del apetito y descenso del gasto energético en
reposo.
Conclusiones

77. Conclusiones
5) La ingesta moderadamente alta de proteína y la
reducción del índice glucémico dentro de una dieta
habitual favorece el mantenimiento de peso, evitando la
recuperación del peso perdido y de la masa grasa
específicamente.

78. Abete I et al., Arch Med Res. 2009 May;40(4):306-10. 2009
Inflammatory state and stress condition in weight-lowering Lys109Arg LEPR gene polymorphism carriers.

79. Goyenechea E et al .(Diabetes Res; 2008)Goyenechea E et al .(Diabetes Res; 2008)
Enhanced short-term improvement of insulin response to a low-caloric diet in
obese carriers the Gly482Ser variant of the PGC-1alpha gene

80. Goyenechea E et al .(Diabetes Res; 2008)Goyenechea E et al .(Diabetes Res; 2008)
Enhanced short-term improvement of insulin response to a low-caloric diet in
obese carriers the Gly482Ser variant of the PGC-1alpha gene

81. Goyenechea E et al .(Diabetes Res; 2008)
Enhanced short-term improvement of insulin response to a low-caloric diet in
obese carriers the Gly482Ser variant of the PGC-1alpha gene

82. Goyenechea E et al .(Br. J Nutr. 2006)
Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and
peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

83. Goyenechea E et al .(Br. J Nutr. 2006)
Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and
peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

84. Goyenechea E et al .(Br. J Nutr. 2006)
Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and
peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

85. Goyenechea E et al .(Br. J Nutr. 2006)
Weight regain after slimming induced by an energy-restricted diet depends on interleukin-6 and
peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms

86. Crujeiras AB et al. (OMICS. 2008)
Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear
cells in response to a low-calorie diet: a nutrigenomics study.

87. Crujeiras AB et al. (OMICS. 2008)
Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear
cells in response to a low-calorie diet: a nutrigenomics study.

88. Crujeiras AB et al. (OMICS. 2008)
Crujeiras AB et al. (OMICS. 2008)
Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear
cells in response to a low-calorie diet: a nutrigenomics study.

89. Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction
Crujeiras AB et al. (Eur J Clin Invest 2008)

90. Crujeiras AB et al. (Eur J Clin Invest 2008)
Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction

91. Crujeiras AB et al. (Eur J Clin Invest 2008)
Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction

92. Goyenechea E et al. (Ann Nutr Metab. 2008)
A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects

93. Goyenechea E et al. (Ann Nutr Metab. 2008)
A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects

94. Goyenechea E et al. (J Nutrigenet Nutrigenomics. 2008)
Expression of two inflammation-related genes (RIPK3 and RNF216) in mononuclear cells is
associated with weight-loss regain in obese subjects.

95. Goyenechea E et al. (J Nutrigenet Nutrigenomics. 2008)
Expression of two inflammation-related genes (RIPK3 and RNF216) in mononuclear cells is
associated with weight-loss regain in obese subjects.

96. SPAIN
33%
11%
PORTUGAL
33%
9%
FRANCE
24%
7%
IRELAND
31%
8%
NETHERLANDS
29%
10%
U. K.
30%
12%
BELGIUM
31%
9%
DENMARK
31%
8%
SWEDEN
33%
7%
LUXEMBOURG
27%
9%
ITALY
30%
7% GREECE
35%
11%
GERMANY
35%
11%
AUSTRIA
32%
10%
FINLAND
33%
10%