Undernutrition Early in

Life
Obesity Later in Life
And Adult Metabolic
Syndrome
Prof. Emanuel Lebenthal, MD
Yogyakarta, Indonesia
December, 2007 8

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Undernutrition Early in Life

And Metabolic Syndrome
Barker hypothesis
Inutero malnutrition
Small for gestational age newborn
Hypertension, Diabetes, Cardiovascular disease
in adults
Barker et al, N Eng J Med, 353: 1802-9,2005

Mechanisms of Undernutrition Early

in Life
And Metabolic Syndrome
Developmental plasticity
Fetal origins hypothesis
Fetal programming
Thrifty phenotype hypothesis
Lebenthal E, Bier M, J of Nutr, 137: 1073-75,2007

Developmental plasticity

Malnutrition inutero
critical period
Altered phenotype for life
Limited postnatal adaptability
Metabolic disease vulnerability
Bateson P, J of Nutr 137:1060-62,2007

Fetal origins hypothesis

Alterations in fetal programming
Genes and environment
(a) energy mobilization
(b) allocation
(c) fuel partitioning

Cellular memory to lifespan

Tradeoff adaptation vs. disease
Environmental plasticity
Ellison PT, Am J Hum Biol 17: 113-18,2005

Fetal programming

Specific genetic endowments

Latent capacities
Malnutrition inutero
Stunting
Forecast maladaptation to affluent
environment
Vulnerability to adult phenotype of disease
Bateson P, J of Nutr 137:1060-62,2007

Thrifty phenotype hypothesis

Epigenetic modifications of gene
expression
Fetus adaptation
(a) cellular
(b) metabolic
(c) physiological
Barker et al, N Eng J Med, 353: 1802-9,2005

Undernutrition Early in Life and

hypertension

Low nephron number

Increase in postnatal body mass
Excretory overload
Nephron response
Proximal tubular hypertrophy
Bagby SP: J Nutr 137: 1066-1072,2007

Proximal tubular hypertrophy and

hypertension

Afferant dilatation
Efferant constriction
Glomerular capillary pressure
Single nephron GFR
Renin /Angiotension Activation
Bagby SP: J Nutr 137: 1066-1072,2007

Thrifty phenotype loci of plasticity

Gene polymorphism
(a) peroxisome proliferator receptor protects
diabetes
(b) K121Q glycogen-1 gene polymorphism
diabetes and hypertension
(c) angiotensin converting enzyme promotes
diabetes and cardiovascular disease
Kubaszck A et al, J Clin Endo Meta, 89: 2044-7,2004.
Eriksson, JB, J Nutr, 137: 1063-65, 2007.

Undernutrition early in life and Type

2 Diabetes
Small for gestational age body size
Interaction early compromise growth and
genotype
Compensatory growth after 3-4 years
Thrifty genes (polymorphism) depend on
body size
Insulin resistance Diabetes
Eriksson, JB, J Nutr, 137: 1063-65, 2007.

Poverty, malnutrition, underdevelopment

and cardiovascular disease (south Africa)

Early undernutrtion, (23%)

Reduced postnatal leptin surge
Obesity in African women (58.5%)
Westernized, urban processed food
Insulin resistance
Cardiovascular diseases.

Vorster HH, Kruger A: Cardiovasc J Afr 18: 321-2, 2007.

Possible causes of the nutrition transition and the emergence

ng countries. Adapted from Martorell and Stein, 2001, and Popkin,
.1994

Therima
Kasih