Adipose tissue and arterial changes in young children

Cardiovascular disease (CVD) is the leading cause of death worldwide. Although the disease becomes apparent later in life, atherosclerosis already begins early in life. Currently it remains largely unknown whether CVD risk factors impact the vascular walls already early in childhood. Moreover, CVD risk factors in early life could be different from the classical risk factors in adulthood. In this thesis we studied specific determinants of vascular wall properties in healthy young children. We showed that children who had been exclusively breastfed in infancy for three to six months had a thicker wall of the carotid artery compared to children exclusively formula fed. Breastfeeding, rich in cholesterol, is suggested to ‘program’ cholesterol metabolism to lower concentrations later in life. The thicker arterial wall associated with breastfeeding might be a reflection of high cholesterol exposure early in life. We also showed that compared with formula fed children, children breastfed for less than 3 months, had higher leptin concentrations. Higher 3-year leptin was associated with higher 7-year fat mass, but this association was less strong in children who had been breastfed longer. These results suggest that breastfeeding increases leptin sensitivity. Leptin is a regulator of energy-intake/expenditure balance and the observed increased leptin sensitivity might explain the lower adiposity associated with breastfeeding. An important CVD risk factor in adults is inflammation. In this study we obtained physician diagnoses of allergies and infections and asked for parental history of allergies. Although infections were not associated with the vascular characteristics, children with an allergic constitution had thicker arterial walls compared to children without parental allergies or an allergy diagnosis. We also pointed out the familial impact of CVD risk by showing thicker and stiffer arterial walls in children with higher parental blood pressure. Early life growth pattern has been suggested to affect both later life fat distribution and CVD risk. We showed that excess weight gain in the first 3 months of life was associated with higher adiposity in early childhood. Particularly in children born relatively small, excess weight gain led to stiffer arteries and a more adverse metabolic profile. In adults, overweight is an established CVD risk factor. We found that at 5-years of age, higher adiposity already was associated with thicker and stiffer arterial walls. Moreover, a larger gain in abdominal fat during childhood was associated with a larger increase in arterial wall thickness and stiffness. In effort to explain the vascular consequences of adiposity, we evaluated the roles of adipocytokines, the glucose and lipid metabolism and blood pressure. With more adiposity, the adipocytokines cathepsin-S, chemerin and leptin were higher, in addition to disturbances of the classical CVD risk factors such as insulin resistance, LDL cholesterol and blood pressure. Although the adipocytokines were not clearly associated with vasculature, glucose and blood pressure slightly were. Whereas the vascular consequences of the adipocytokines are minimal, the glucose metabolism could be slightly more important for the vasculature of young children