Cigarette Smoke During Breastfeeding in Rats Changes Glucocorticoid and Vitamin D Status in Obese Adult Offspring

Abstract

Maternal smoking increases obesogenesis in the progeny. Obesity is associated with several hormonal dysfunctions. In a rat model of postnatal tobacco smoke exposure, we previously reported increased central fat depot and disruption of some hormonal systems in the adult offspring. As both glucocorticoids and vitamin D alter lipogenesis and adipogenesis, here we evaluated the metabolism of these two hormones in visceral adipose tissue (VAT) and liver by Western blotting, and possible associations with lipogenesis biomarkers in adult rats that were exposed to tobacco smoke during their suckling period. At postnatal day (PN) 3, dams and offspring of both sexes were exposed (S group) or not (C group) to tobacco smoke, 4 × 1 h/day. At PN180, corticosteronemia was lower in S male and higher in S female offspring, without alterations in peripheral glucocorticoid metabolism and receptor. Adrenal ACTH receptor (MC2R) was higher in both sexes of S group. Despite unchanged serum vitamin D, liver 25-hydroxylase was higher in both sexes of S group. Male S offspring had higher 1α-hydroxylase, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) in VAT. Both sexes showed increased ACC protein content and reduced sirtuin mRNA in liver. Male S offspring had lower liver peroxisome proliferator-activated receptor-α. Tobacco exposure during lactation induced abdominal obesity in both sexes via distinct mechanisms. Males and females seem to develop HPA-axis dysfunction instead of changes in glucocorticoid metabolism and action. Lipogenesis in VAT and liver, as well as vitamin D status, are more influenced by postnatal smoke exposure in male than in female adult rat offspring.

Keywords: adipose tissue; cigarette smoke; lactation; liver; programming.

Figure 1

Representative photomicrographs (×40; hematoxylin-eosin) of the visceral adipose tissue of adult rats programmed by smoke exposure during the lactation. (A) morphology of C and S males; (B) morphology of C and S females; (C) retroperitoneal adipocyte area size of C and S males; (D) retroperitoneal adipocyte area size of C and S females. Both groups showed standard morphology, with no changes in the adipocyte area. Groups: C—CONTROL and S—SMOKE (n = 6 rats/group).

Figure 2

Representative photomicrographs (×60; hematoxylin-eosin) of the liver of adult rats programmed by smoke exposure during the lactation period. (A) morphology of C and S males; (B) morphology of C and S females. Both groups presented typical architecture, with no inflammatory cell infiltrate or drops of lipids in their cytoplasm. Groups: C—CONTROL and S—SMOKE (n = 6 rats/group).

Figure 3

Corticosterone and ACTH receptor content in adult rats programmed by smoke exposure during the lactation period. Corticosterone levels in the plasma (A—male; B—female) and melanocortin 2 receptor (MC2R) content in the adrenal gland (C—male; D—female). Groups: C—CONTROL and S—SMOKE. alues are given as means ± S.E.M. of 8–10 rats/group. * p < 0.05 significant difference between S vs. C.

Figure 4

Glucocorticoid metabolism and action of adult rats programmed by smoke exposure during the lactation period. In the adipose tissue: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1; A—male; C—female) and glucocorticoid receptor alpha (GRα; B—male; D—female); In the liver: 11β-HSD1 (E—male; G—female) and GRα (F—male; H—female). Groups: C—CONTROL and S—SMOKE. Values are given as means ± S.E.M. of 5–7 rats/group.

Figure 5

Vitamin D status of adult rats programmed by smoke exposure during the lactation period. Hepatic 25-hydroxylase (CYP2R1; A—male; D—female); Plasma 25-hydroxyvitamin D (25(OH)D) (B—male; E—female); Visceral fat 1α-hydroxylase (CYP27B1; C—male; F—female). Groups: C—CONTROL and S—SMOKE. Values are given as means ± S.E.M. of 5–10 rats/group. * p < 0.05 significant difference between S vs. C.

Figure 6

Lipogenesis in visceral adipose tissue of adult rats programmed by smoke exposure during the lactation period. Acetyl-CoA carboxylase (ACC; A—male; C—female); fatty acid synthase (FAS; B—male; D—female). Groups: C—CONTROL and S—SMOKE. Values are given as means ± S.E.M. of 4–7 rats/group. * p < 0.05 significant difference between S vs. C.

Figure 7

Lipogenesis in the liver of adult rats programmed by smoke exposure during the lactation period. Sirtuin-1 mRNA expression (Sirt1; A—male; E—female); peroxisome proliferator-activated receptor alpha (PPAR-α; B—male; F—female); acetyl-CoA carboxylase (ACC; C—male; G—female); fatty acid synthase (FAS; D—male; H—female). Groups: C—CONTROL and S—SMOKE. Values are given as means ± S.E.M. of 5–7 rats/group. * p < 0.05 significant difference between S vs. C.