INCREASED FAT INTAKE DURING LACTATION MODIFIES HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSIVENESS IN DEVELOPING RAT PUPS - A POSSIBLE ROLE FOR LEPTIN

High fat feeding reportedly enhances hypothalamus-pituitary-adrenal (H PA) responses to stress in adult rats. The present study tested whethe r elevated fat intake during suckling could have short and/or long las ting consequences on HPA regulation in the offspring. Mothers were fed either a control(C; 5% fat) or high fat (HF; 20% fat) diet during the last week of gestation and throughout lactation. After weaning (day 2 1), pups from C and HF mothers were fed a chow diet. Offspring from bo th C- and HF-fed mothers were tested for ACTH and corticosterone respo nses to stress on postnatal days 10 and 35. Rie found that HF feeding produced higher lipid levels in the milk of HF compared with C lactati ng rat dams and that offspring of these mothers had significantly incr eased retroperitoneal fat pad weight and relative adipose mass on day 21 as well as elevated plasma leptin levels on days 10 and 21 of age. After weaning, pups from the HF mothers had lower plasma leptin levels than those from C mothers. Maternal dietary fat affected HPA responsi veness in the offspring in an age-related manner. Neonatal pups (day 1 0) from the HF mothers exhibited a reduction in the ACTH and corticost erone responses to ether stress. However, in 35-day-old offspring from HF-fed dams, stress-induced ACTH secretion was increased compared wit h that in pups from the C-fed mothers. These results demonstrate that maternal diet and increased fat intake through the milk are important regulators of HPA responsiveness in neonates and prepubertal rats. Dur ing neonatal life, the blunted stress responsiveness seen with elevate d fat intake and the resulting high leptin levels might protect the pu ps from excessive HPA activation. After removal of the maternal dietar y influence and reduced leptin levels, enhanced ACTH stress responses are observed as in adult rats fed a HF diet. Because of the inverse re lationship between plasma levels of leptin and HPA responses in pups, the possibility exists that the effects of the HF diet on stress respo nsiveness are mediated by changes in leptin exposure during developmen t.