Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation

Abstract

Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

Keywords: development; exercise; leptin; maternal diet; obesity.

Fig. 1.

Body weight and food intake of dams during gestation and male pups' body weight before weaning. A: dams' body weight during gestation. B: dams' food intake per week during gestation. C: male pups' body weight before weaning. CHOW, n = 12; HF, n = 12. *P < 0.05 vs. CHOW group.

Fig. 2.

At 4 wk of age, male offspring from CHOW or HF dams were left sedentary or given free access to exercise on a running wheel. RW groups were allowed to exercise for 3 wk, after which time their wheels were removed and all rats remained sedentary. A: body weight during and after running. B: daily food intake during and after running. C: daily running revolution during 3 wk of running. *Main effect of maternal HF diet, P < 0.05 vs. maternal chow diet. #Main effect of running, P < 0.05 vs. sedentary group.

Fig. 3.

Adipose depots (A and B) at 14 wk of age and plasma leptin concentration at 6 wk (after 17 days running) (C) and 16 wk (sedentary for 9 wk after running) (D) of age. ^a,bGroups with different superscript letters differ from each other at P < 0.05 level.

Fig. 4.

Glucose tolerance test (2.0 g/kg, oral gavage) at 7 wk (right after 3 wk running) (A and C) and 10 wk (sedentary for 3 wk after running) (B and D) of age. Blood glucose (A and B) and plasma insulin (C and D) were determined for 2 h after administration of glucose. The integrated area under the curve (AUC) was determined for glucose and insulin using the trapezoidal method. *Main effect of maternal HF diet, P < 0.05 vs. maternal CHOW diet. #Main effect of running, P < 0.05 vs. sedentary group. $P < 0.05, HF-SED vs. other three groups. C-S, CHOW-SED; C-R, CHOW-RW; H-S, HF-SED; H-R, HF-RW.

Fig. 5.

At 14 wk of age, rats received intracerebroventricular injection of saline or 10 μg leptin, and food intake was monitored at 4 h (A and C) and 22 h (B and D). Cumulative food intake (A and B) and suppression of food intake in response to leptin (C and D) were analyzed. *P < 0.05 vs. saline group; ^a,bGroups with different superscript letters differ from each other at P < 0.05 level.

Fig. 6.

At 17 wk of age, after overnight fast, rats received intracerebroventricular injection of saline (n = 3) or 10 μg leptin (n = 3) at dark onset and were decapitated 3 h later. p-STAT3 and t-STAT3 were measured in ARC by Western blot. A: band for p-STAT3. B: p-STAT3/t-STAT3 ratio (compared with leptin-injected rats in CHOW-SED group). *P < 0.05.

Fig. 7.

Gene expression in the hypothalamus. At 14 wk of age, after a 4-h fast, rats were killed by decapitation (n = 6 per group). Tissue from the paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMN), dorsomedial hypothalamic nucleus (DMN), and lateral hypothalamus (LH) were punched and assayed by quantitative RT-PCR. BDNF, brain-derived neurotropic factor; MC4R, melanocortin-4 receptor; LepRb, leptin receptor-b; NPY, neuropeptide Y; POMC, proopiomelanocortin; MCH, melanin concentrating hormone. Expression level of each gene examined was normalized to β-actin mRNA levels. ^a,b,cParameters with different superscript letters differ from each other at P < 0.05 level.