Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity

Abstract

Maternal high-fat (HF) diet throughout gestation and suckling has long-term consequences on the offspring's metabolic phenotype. Here we determine the relative contribution of pre- or postnatal maternal HF diet on offspring's metabolic phenotype. Pregnant Sprague-Dawley rats were maintained on normal chow or HF diet throughout gestation and suckling. All litters were cross-fostered to chow or HF dams on postnatal day (PND)1, resulting in four groups. Body weight, body composition, and glucose tolerance were measured at weaning and in adulthood. Leptin sensitivity was assessed by signal transducer and activator of transcription (STAT)3 activation on PND10 and PND21. Pups cross-fostered to HF dams gained more body weight than chow pups by PND7 and persisted until weaning. Postnatal HF pups had greater adiposity, higher plasma leptin concentration, impaired glucose tolerance, and reduced phosphorylated STAT3 in response to leptin in the arcuate nucleus at weaning. After weaning, male offspring cross-fostered to HF dams were hyperphagic and maintained greater body weight than postnatal chow pups. Postnatal HF diet during suckling continued to impair glucose tolerance in male and female offspring in adulthood. Maternal HF diet during suckling has a greater influence in determining offspring's metabolic phenotype than prenatal HF diet exposure and could provide insight regarding optimal perinatal nutrition for mothers and children.

FIG. 1.

Body weight and body composition of offspring before weaning. Male (A) and female (B) offspring were weighed on PND1, 7, 14, and 21. Fat tissue as a percentage of body weight (BW) was measured in male (C and E) and female (D and F) offspring on PND10 (C and D) and 21 (E and F). n = 8 litter per group. *Main effect of postnatal HF diet, P < 0.05 vs. postnatal CHOW diet. #Main effect of postnatal HF diet on visceral fat percentage, P < 0.05 vs. postnatal CHOW diet. **Main effect of postnatal HF diet on total and subcutaneous fat percentage, P < 0.05 vs. postnatal CHOW diet.

FIG. 2.

Glucose tolerance test (2.0 g/kg, oral gavage) results for male (A and C) and female (B and D) offspring on PND23. Blood glucose (A and B) and plasma insulin (C and D) were determined for 2 h after oral administration of glucose. The integrated AUC (inset) was determined for glucose and insulin using the trapezoidal method. CHOW-CHOW (C-C), n = 4; CHOW-HF (C-H), n = 4; HF-CHOW (H-C), n = 5; HF-HF (H-H), n = 5. *Main effect of postnatal HF diet, P < 0.05 vs. postnatal CHOW diet. #P < 0.05, HF-CHOW vs. CHOW-CHOW.

FIG. 3.

Western blot of pSTAT3 in MBH in male (A) and female (B) offspring on PND10. The pSTAT3-to-total (t)STAT3 ratio (compared with leptin-injected pups in CHOW-CHOW group) was calculated in male (C) and female (D) offspring. The pups were injected with saline (n = 3) or leptin (n = 5) in each group. *P < 0.05 vs. saline group. #P < 0.05 vs. CHOW-CHOW group.

FIG. 4.

Western blot of pSTAT3 and total (t)STAT3 in ARC in male (A) and female (B) offspring on PND21. The pSTAT3-to-tSTAT3 ratio (compared with leptin injected pups in CHOW-CHOW group) was calculated in male (C) and female (D) offspring. The pups were injected with saline (n = 3) or leptin (n = 5) in each group. *P < 0.05 vs. saline group. #P < 0.05 vs. CHOW-CHOW group.

FIG. 5.

Body weight in adult male (A) and female (B) offspring at age 12 weeks. Fat for males (C) and females (D) is expressed as the weight of the dorsosubcutaneous and inguinal (SC) and retroperitoneal (RP) fat pad as a percentage of body weight (BW). n = 8 per group. *Main effect of postnatal HF diet, P < 0.05 vs. postnatal CHOW diet. #Main effect of postnatal HF diet on subcutaneous fat, P < 0.05 vs. postnatal CHOW diet.

FIG. 6.

Glucose tolerance test in males (A and C) and females (B and D) at age 10 weeks. Blood glucose (A and B) and plasma insulin (C and D) were determined for 2 h after oral administration of glucose. The integrated AUC (inset) was determined for glucose and insulin using the trapezoidal method. n = 5 per group. *Main effect of postnatal HF diet, P < 0.05 vs. postnatal CHOW diet; #P < 0.05 vs. CHOW-CHOW group. C-C, CHOW-CHOW; C-H, CHOW-HF; H-C, HF-CHOW; H-H, HF-HF.