The effects of birth weight and accelerated weight on body composition and appetite regulation

Abstract

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.