Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rats

Abstract

We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8 microg/100 g body weight, subcutaneously) for the first 10 d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150 d old. Food intake was higher in the Lep group (approximately 14 %, P<0.05) from day 133 onwards, and body weight was higher (approximately 10 %, P<0.05) from day 69 onwards, compared with the control group. At 150 d of age, the rats were tested for food intake in response to either leptin (0.5 mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (-40 %, P<0.05), hyperleptinaemia (+78 %, P<0.05), hyperinsulinaemia (+100 %, P<0.02), hypertriacylglycerolaemia (+17 %, P<0.05) and a higher protein content in the body (+16 %, P<0.05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.