Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation.
OBJECTIVE
To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance.


METHODS
Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age.


RESULTS
Plasma leptin levels were raised two-fold on days 16-18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11beta-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels.


CONCLUSIONS
The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.
Stocker
C
C
Clore Laboratory, University of Buckingham, Buckingham, UK.
O'Dowd
J
J
Morton
N M
NM
Wargent
E
E
Sennitt
M V
MV
Hislop
D
D
Glund
S
S
Seckl
J R
JR
Arch
J R S
JR
Cawthorne
M A
MA
D000818:Animals; D001724:Birth Weight / Q000187:drug effects*; D001786:Blood Glucose; D018753:Diet, Protein-Restricted; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D007774:Lactation / Q000502:physiology*; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects*
D001786:Blood Glucose; D004041:Dietary Fats; D020738:Leptin