Maternal diet and disease 02/04 Flashcards
What is the concept of developmental fetal programming?
Both maternal diet and the hormonal environment in which the fetus gestates, along with early post-natal life, can alter it’s development and cause critical adapatations with lifelong effects due development of physiological systems to increase disease risk profile in later life.
Adverse in-utero enivornment during critical growth periods causes structural changes in organs, which interacts with metabolic dysfunction and poor childhood growth to cause later life disease
What is metabolic syndrome?
Metabolic syndrome is a group of risk factors – high blood pressure, high blood sugar, high triglycerides, low HDL cholesterol, and belly fat – that increases risk of heart disease and diabetes
Which adulthood conditions are associated with low birthweight?
Abdonminal obiesity
High blood pressure
Insulin resistance
Dyslipidemia
These are all associated with metabolic syndrome and converge onto increased risks for CHD and stroke
What was the dutch hunger winter study?
During the 2nd world war, calories were restricted from around 2000-2500 to 400-800 per day. Clinical follow ups found that adults exposed to famine during
Early gestation showed atherogenic lipid profiles, obeisity increased risk of CHD -independent of their birth weight showed impaired glucose tolerance
Late gestation showed impaired glucose tolerance
Conclusions from the study are limited however as diets were very different during this time period. Results do hold in contemporary cohort studies, though.
What are the two greatest developmental risk factors for CVD and metabolic syndrome in adult life?
Low birthweight or poor nutrition in pregnancy accompanied by rapid catch-up growth in early infancy is associated with increased risk of CVD and metabolic syndrome in adult life.
What is the thrifty phenotype hypothesis?
The ‘thrifty phenotype hypothesis’ states that growth restriction/malnutrition in utero leads to fetal adaptations which favour post natal survival in a similarly deprived environment, and that disease ensues when the diet is ‘richer’ than the utero diet.
What is the relationship between breast feeding and obesity?
Breast feeding instead of formula feeding may reduce obesity by 22% - however these are only observational.
However, it may derive its protective mechanisms from:
- Reduced intake compared to bottle-fed babies
- Slower weight gain in breast-fed babies
- Milk-borne hormones may be protective (leptin/insulin)
- Composition of formula (high protein) affects growth
How may baby formula milk lead to accelerated post natal weight gain?
It is very high in protein, causing high levels of insulinogeneic amino acids in the tissue and the plasma. This causes increased insulin secretion, resulting in adipogenic activities and weight gain.
What is the general relationship between birthweight and risk of obiesity?
U shape
Which maternal weight factor has the strongest influence on adult BMI
Pre-pregnancy BMI of the mother strongly correlates with BMI of offspring at 32 years of age. Gestational weight gain also shows positive correlation. There is a similar relationship between maternal factors and waist circumference.
The same relationship holds between blood pressure and maternal factors.
The strongest evidence comes from a study comparing macrosomia and obeisty in adult offspring with mothers before and after a bariatric surgery (gastric band).
Leptin
A hunger inhibiting hormone secreted by adipocytes. It binds to receptors in the arcuate nucleus of the hypothalamus to regulate appetite. Much like insulin, obesity is associated with increased levels of leptin and decreased sensitivity to leptin.
What is the effect of maternal obesity on Leptin?
Males and females with obese mothers have a much higher food intake once weened.
Control m+f mice show reduced food intake when given leptin injection. This is not seen in obsese mother m+f mice - leptin insenstivity. They also do not show the normal body weight reduction in reponse to leptin injection.
There is also a much greater post natal leptin surge. This is an important developmental signal for the hypothalamus, and it’s alteration may affect development of hypothalamic circuitry required for normal appetite regulation.
What role does leptin play in neurodevelopment?
Mice KO for leptin gene show reduced development of the dendritic arbors of the arcuate nucleus within the hypothalamus (part of networks that regulate appepite, including vagus nerve projecting to enteric system).
If these mice are given exogeneous leptin during a critical neonatal development period, then development of arcuate nucleus will be restored. There is normally a leptin surge during this period. Giving during adulthood or after critical period has no influence.
What are the developmental origins of leptin resistance?
Excessive Weight Gain & Adiposity of the mother leads to fetal hyperleptinaemia and hyperinsulinaemia - leading to selective leptin resistance.
It is selective because the metabolic functions of leptin are lost, but the systemic functions are retained. Increased leptin therefore causes hypertension through systemic pathways, and resistance in metabolic pathways cause hyperphasia and obesity.
What is the link between senescence and early development?
Catch up growth is associated with shortening telomeres in the kidneys male mice.
