Maternal nicotine exposure enhances adipose tissue angiogenic activity in offspring: Sex and age differences

Maternal nicotine exposure during pregnancy and lactation (NIC) is associated with dysfunction of white adipose tissue (WAT). We focused on the NIC-induced WAT angiogenesis and explored its sex and age differences. Pregnant rats were randomly assigned to NIC (1.0 mg/kg nicotine twice per day) or control groups. Distribution and density of blood vessels were observed. Angiogenesis-related genes were tested at 4, 12 and 26 weeks to estimate angiogenic activity. In vitro, nicotine concentration- and time-response experiments (0-50 μM) were conducted in 3T3-L1. Lipid accumulation and angiogenesis-related genes were tested. NIC increased the blood vessels in inguinal subcutaneous WAT (igSWAT) and gonadal WAT (gWAT) of 26-week-aged male and 4-week-aged female offspring. In males, nicotine showed higher angiogenic activity at 26 weeks than at 4 weeks in igSWAT and gWAT. In females, nicotine's angiogenic activity was higher at 4 weeks than 26 weeks in igSWAT and gWAT. In vitro, nicotine promoted adipocyte differentiation, and increased the expression of angiogenesis-related genes in concentration- and time dependent manners. In conclusion, NIC-induced enhancement of angiogenic activity in WAT presented sex and age differences: nicotine showed higher angiogenic activity in adulthood than in childhood of male offspring, but the converse results were observed in female offspring.