The link between early life and development of metabolic disorders and
obesity in later life has been the focus of many studies over the past
decades. Fetal life and early infancy are two of the most critical periods of
physiological and metabolic development and plasticity, and thus, are
periods whereby a stimulus can cause long term consequences on the
health of an individual (developmental programming).
Accelerated weight gain during early life per se or in combination with
extreme birth weights (low/high birth weight) have been postulated as factors
that can affect the development of individuals with later consequences in
health. However, there is not a clear understanding of the specific
contribution at different ages to impaired health neither of the mechanisms
involved in these alterations.
In this thesis, I used an isogenic murine model with natural birth weight
variation within a normal range to investigate the effects of extreme birth
weights on body composition and appetite regulation at different stages of
life. I compared low and high birth weights phenotypes during lactation, at
the time of weaning, and a young adulthood as well as early matured age.
Mice were challenged to a moderate high fat diet for 12 weeks after weaning
in order to assess the effects of both birth weight and a hypercaloric feed on
body composition and hypothalamic neural activity.
At weaning, adiposity was positively related to birth weight and weight gain
but negatively related to growth rate. Low birth weight male mice (LBWm)
had a lower plasma glucose concentration but similar levels of insulin to High birth weight male mice (HBWm), indicating a degree of hyperinsulinemia.
Low birth weight females (LBWf) were hyperinsulinemic and hyperglycemic
compared to High birth weight females (HBWf). There was an upregulation
in the expression of genes related to insulin signaling, adipogenesis/lipid
metabolism and thermoregulation in Subcutaneous Adipose Tissue (SAT) of
LBWm mice compared to HBWm mice but the contrary was seen in LBWf
mice in respect to their counterpart.
LBWm mice caught up in weight with HBWm mice at younger age than the
equivalent catch up in female mice. Birth weight and diet impacted body fat
patterning and appetite regulation differently in both young males and
females. However, at week 51 of age (early matured age), diet seemed to
override the effects of birth weight on total body fat. LBWm mice tended to
have smaller adipocytes than young and matured HBWm mice, especially
when fed a HF diet, and this pattern was independent of fat mass.
In conclusion, the current study suggests that extreme birth weights in an
isogenic mouse model (within natural birth weight variation), as well as
postnatal nutrition influenced growth, glucose / lipid metabolism, body fat
patterning and appetite regulation in an age-gender dependent manner.