Evaluation of different effects of postnatal overfeeding on vascular system of male and female rats

  • Autor
  • Kawane Fabricio Moura
  • Co-autores
  • Karine Fagundes Silvino Rodrigues , Carolina Oliveira Gonçalves , Kaio Yuri Morimoto , Isadora Chagas Vercellone , Ernane Torres Uchoa , Fábio Goulart de Andrade , Graziela Scalianti Ceravolo
  • Resumo
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    In recent years incidence of childhood obesity has increased globally.  Besides the metabolic alterations, it has been shown that high body mass index, both in men and women, acts as an independent risk factor for cardiovascular diseases. The study aimed to evaluate the effects of childhood obesity induced by postnatal overfeeding on aortic reactivity and blood pressure in prepubertal and adult rats from both sexes. At postnatal day (PND) 1, Wistar rat were divided into a normal litter (NL, mothers were kept with 5 female and 5 male pups) or small litter (SL, mothers were kept with 2 male and 1 female pup). The rats were evaluated at two time points prepubertal (PND 30 for females and 40 for males due to known sexual maturation differences), and in adulthood (120 for both sex). Body weight (g) and retroperitoneal adipose tissue (fat pad weight/100g of the body n=9-13) were evaluated. The blood pressure means (BPM, mmHg n=6-7) and the heart rate (HR, bpm n=6-7) variable were measured in conscious rats by indirect tail-cuff method. Aorta was removed for wall thickness measurements via histology (n=5, µm), and vascular function was performed via pin myograph.  Concentration-response curves to phenylephrine [Phenyl, 1nM-10µM, n=6, gram force (gf)] or acetylcholine (ACh 0.1nM100µM, n=7 % relaxation) were performed. To understand the role of the NADPH-derived reactive oxygen species, angiotensin-II and aldosterone, apocynin (APO 10 µM), losartan (LOS 1 µM) or spironolactone (SPR 1 µM) were used respectively (CEUA: 112/2020). Prepubertal SL rats had higher body weight (female: NL 76±2 vs SL 91±1, g, p<0.05; male: NL 148±2 vs. SL 185±4, g, p<0.05), and adipose tissue deposition (female: NL 0.09±0.01 vs. SL 0.17±0.01, p<0.05; male: NL 0.17±0.09 vs. SL 0.32±0.03, p<0.05) regardless of sex. Interestingly, there were no differences in these parameters at PND 120 for female NL and SL. In contrast, male SL at PND 120 had higher body weight (NL 419±9 vs SL 462±5, g, p<0.05) and retroperitoneal adipose tissue (NL 1.2±0.9 vs SL 1.6±0.1, p<0.05]). Both female and male SL rats presented increased BPM (female: NL 87.86±2.29 vs SL 99.81±3.20; male: NL 114.9±0.58 vs SL 120.5±1.20) when compared with NL rats, but only SL females presented increased values of HR (NL: 314.60±9.35 vs SL: 357.90±7.05) while males had similar HR between groups (NL: 345.0±5.38 vs SL: 352.7±9.380). Any differences were observed in phenyl-induced contraction in aortas from females at PND 30 and 120. On the other hand, endothelial dysfunction was observed at PND 120 in arteries from SL female rats [Maximum response (Rmax): NL 94±1 vs SL 84±2, % p<0.05]. However, LOS (Rmax: SL 77±1 vs LOS 90±1, % p<0.05) and APO (SL 77±1 vs APO 87±1, % p<0.05] restored endothelial function in these animals. No changes in endothelium-dependent relaxation were observed in arteries from male rats at PND 40 or 120. However, there was an increase in vascular contractility from SL males at PND 40 (Rmax: NL 1.17±0.40 vs SL 1.47±0.06, g, p<0.05), and SPR (SL 1.50 ±0.14 vs SPR 0.93±0.09, g, p<0.05) improved this response, but no differences were observed at PND 120.  Further, the aortic thickness was similar between groups at PND 120 regardless of sex. In conclusion, postnatal overfeeding in rats causes childhood obesity associated with hypertension and vascular dysfunction. These differences were obtained in prepubescent and adult rats, and the respective mechanisms are sex dependent.

     

  • Palavras-chave
  • childhood obesity; vascular dysfunction; sex differences
  • Modalidade
  • Comunicação oral
  • Área Temática
  • Trabalhos originais
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Comissão Organizadora

Gustavo Carvalho
Luiza Malacco
Eliana Hiromi Akamine
Profª Drª Luciana Venturini Rossoni
Ana Paula Couto Davel
José Wilson do Nascimento Corrêa
GIULIA ALESSANDRA WIGGERS
Alice Valença Araújo

Comissão Científica