Neonatal overfeeding (PO) leads to the development of early obesity and cardiovascular dysfunction at adulthood. PPAR? agonist treatment during adult life is able to attenuate the development of obesity. We hypothesized that neonatal treatment with a PPAR? agonist prevent the development of obesity and cardiovascular dysfunction during adult life induced by neonatal overfeeding.
Wistar pregnant rats were maintained in standard conditions until delivery. On PN1 litters were standardized for 9 pups per mother, normal litter (NL). At PN3, a set of litters were reduced for 3 male pups per mother, small litter (SL). During lactation animals were submitted to the treatment with fenofibrate, a PPAR? agonist, (12,5mg/kg diluted in vehicle; F) or its vehicle (DMSO10%SOLUTOL15%H2O; V) forming 4 experimental groups: NL-V(n=6), NL-F(N=5), SL-V(n=6) and SL-F(n=6). On PN120 biometric and cardiovascular parameters were evaluated.
A significant effect of PO was observed in bodyweight, SL-V animals had increased bodyweight compared to NL-V (SL-V 456.6±9.7; NL-V 418.9 ±6.5; p<0,05). In visceral fat, an interaction between PO and treatment was observed (p<0.01), SL-V animals had increased perigonadal fat when compared to NL-V (SL-V 1.3±0.07, NL-V 0.99±0.08, p<0.01), which was reduced when compared to SL-F animals (SL-F 1.0±0.07, SL-V 1.3±0.66, p<0.05). A significant effect of PO was observed in heart and kidney weight (p<0.05), which is more evident in animals treated with vehicle (heart: SL-V 2.2±0.079; NL-V 1.918±0.047; p<0.05). The basal heart rate showed a significant effect of PO and fenofibrate treatment (p<0.05 2), being reduced in SL animals and by fenofibrate. The median blood pressure depressor response to hexamethonium (30 mg/kg,iv), a ganglionic blocker, was exacerbated in the SL-V animals, which lead to a significant interaction between PO and fenofibrate (p<0.05). We conclude that early overfeeding leads to the development of obesity and hyper-sympathetic activity, which is blocked by early treatment with PPAR? agonist.
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