2. Developmental Programming
• Developmental plasticity- Ability of an organism to develop in various
ways, depending on the particular environment or setting
• Developmental programming- Process whereby a stimulus applied in utero
establishes a permanent response in the fetus leading to enhanced
susceptibility to later diseases
• IUGR +/- catchup growth
• due to maternal under or over nutrition or exposure to certain substances(e.g.
endogenous hormones or endocrine disruptors such as BPs)
• impact upon adult health and disease
• Commonly associated with cardiovascular and metabolic disorders:
• Coronary heart disease and hypertension
• Insulin resistance
• Obesity
• Type 2 diabetes
When co-
occurring are
termed
"diabesity"
3. Developmental Programing: Maternal Undernutrition
• Initial evidences from Dutch hunger winter 1944-45
• Dutch population, including pregnant women had to survive on only a few hundred calories/day
for many months
• Follow-up upon individuals in utero during Dutch hunger
winter study
• 1st and 2nd trimester fetal undernutrition
• Adult obesity
• Raised circulating lipids
• Blood clotting factors
• Increased coronary health risks
• Mid, late gestation fetal undernutrition
• Impaired renal function
• Impaired glucose metabolism
Dutch citizens waiting in line for
food during the hunger winter
4. Metabolic Disease and Developmental Programming
• Adult type 2 diabetes and/or obesity
(Diabesity) related to two factors
• NMT Nutrient-mediated teratogenesis
• Focuses upon the quality (concentrations of
nutrients) of maternal diet during gestation
• Deprivation of micronutrients during critical
period
• FMT Fuel-mediated teratogenesis
• Focuses upon quantity of maternal diet during
gestation
• Excess availability of fuel(glucose)
• Diabetic pregnancy
• Postnatal availability of excess nutrients in low
birth weight infant
Teratogenesis= fetal
malformations
5. Developmental Importance of Nutrition
• Protein- multiple roles
• structure of tissues (muscle, bone, etc.)
• transport of molecules, storage and regulation
• antibodies, hormones, enzymes, essential amino acids
• Essential Micronutrients during Gestation
• Vitamin B12-nerve cell health, production of DNA and RNA
• Sources: animal products
• Folic Acid- proper brain function, also works with B12 for normal red blood cell production
• Sources: dark greens
• Omega-3 (DHA)•-crucial in brain function, anti-inflammatory, normal growth and development
• Sources: fish, oilseed meals
• Other key micronutrients
• Zinc-cell division, cell growth, wound healing, breakdown of carbs and olfactory senses
• Sources :meat, some seafood, legumes, nuts
• Iron-normal blood production
• Sources: red meat, dark greens
• Vitamin D- reduces risks of gestational diabetes, preterm birth, preeclampsia, and infections
• Sources: fatty fish (salmon or tuna), fish liver oils, beef liver, eggs
6. Maternal Protein Intake
• Protein restriction during gestation(rodent model)
• Decreased pancreatic β- cell mass at birth
• Reduced insulin secretion later in life (reduced proliferation and increased apoptosis)
• Can lead to the development of diabetes
• Rise in hepatic triglycerides
• Risk of atherosclerosis
• Hepatic expression of lipogenic enzymes
• Favor fat synthesis
• Excessive fat accumulation
• Postnatal food preferences for high fat foods
7. One-Carbon Metabolism
One-carbon Metabolism refers to a group of biochemical reactions involved in amino acid and nucleotide metabolism
which involves the transfer of one-carbon groups which are volatile and need to be attached to something while being
processed.
• Dietary folate is converted to MTFR using B12 as a co-factor
• Methylated folate provides methyl groups to convert homocysteine to methionine (universal methyl group donor for all methylation
reactions in body)
9. Thin-Fat Indian Phenotype
• Paternal size will influence skeletal measurements and
maternal micronutrient intake will strongly determine
fetal size and baby's adiposity
• Thin-fat Indian phenotype:
• lower birth weight, increased visceral adiposity, altered lipid and
glucose metabolism
• can increase risk of insulin resistance and diabesity
• Strong evidence found in studies of B12 deficiency especially
when paired with over availability of folate – PMNS India
• Wistar rat model- replicated phenotype of in offspring B12
deficient dams
• showed imbalance between pro and anti-inflammatory cytokines
• Increased levels of cortisol, and leptin
• Decreased levels of adiponectin
• Adiponectin -regulation of glucose levels and fatty acid metabolism
Indian mother and child
with child displaying excess
adiposity
11. Maternal Micronutrient Intake
• Subclinical micronutrient deficiency in rural Gambia
• Vitamin B12, folic acid, Vitamin B6, Vitamin D, selenium,
iron, chromium, zinc.
• Gambia- nutrition patterns affected by season
• Rainy season- low nutrient availability
• Long dry season- normal nutrient availability
• High incidence of micronutrient deficiency in rainy season
• Resultant offspring:
• Low birth weight
• Childhood morbidity
• Childhood mortality
Gambian mother and
children eating a meal
12. Prenatal Omega-3 (DHA)
• Docosahexaenoic acid (DHA) omega -3
polyunsaturated fatty acids (n-3 PUFA)
• DHA has been demonstrated to have role in
prevention of insulin resistance and decrease
CVD risk (animal models)
• DHA availability during perinatal period
associated with long term cognitive and visual
development
• DHA has a critical role in OCM
• Altered DHA levels- excess methyl group
availability for DNA and histone
methylation leading to chromatin
remodeling and altered gene expression
14. Role of Micronutrients in Omega-3 (DHA) Metabolism
• OCM –conversion of folate via B12 coenzyme
• produces methionine which is precursor for SAM, methyl group donors from
SAM are transferred by PEMT to DHA (also DNA and histones)
• Maternal micronutrient imbalance (rat model)
• Excess folate and less B12
• influence n-3 PUFA metabolism(OCM)
• Decrease plasma and placental DHA levels
• Increased placental pro-inflammatory cytokine levels
15. Disease Development: Diabetes
• Genetics
• Fetal Programming
• Maternal nutrition
• +/- exposure to
endogenous
hormones, or
endocrine distuptors
Susceptibility
Precipitating
Factors
Accelerating
Factors
Type 2
Diabetes
• Lifestyle
• Nutrition
• Inactivity
• Psychosocial stress
• Rapid childhood
growth
• inflammation
• Glucotoxicity
• decrease in insulin secretion and an
increase in insulin resistance due to
chronic hyperglycemia.affects the
secretion of β-cells.
• Lipotoxicity
• metabolic syndrome that results from the
accumulation of lipid intermediates in non-
adipose tissue, leading to cellular
dysfunction and death.
