Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure

Abstract

Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C -standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N -standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (C51%), catecholamine content (C37%), and serum 25-hydroxyvitamin D 3 (C76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (K37%) and higher in liver (C42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

Maternal high‐fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning

“…Leptin gene expression was quantified as previously described (Nobre et al 2011). Total RNA was isolated from inguinal adipose tissue using a commercial kit (RNeasy lipid tissue mini kit, Qiagen, Hilden Germany).…”

Calcium reduces vitamin D and glucocorticoid receptors in the visceral fat of obese male rats

“…The concentration of calcium used here is twice the amount recommended to rodents (5 g/kg of chow) and is based on the recommendation for calcium supplementation in humans. We previously published that, at this concentration, calcium does not seem to change diet palatability since food intake, body mass, fat depot, serum leptin as well as hypothalamic leptin signaling of lean control rats are not altered by this calcium-rich diet when compared with control animals with no calcium supplementation (Nobre et al 2011(Nobre et al , 2012.…”

“…Previous data from our group have demonstrated that a calcium-supplemented diet is able to decrease visceral adiposity and 25(OH)D levels in two obesity models (early weaning and postnatal nicotine exposure), which can be associated (Nobre et al 2012(Nobre et al , 2016 or not (Nobre et al 2011) with reduction in food intake. These data lend support to the notion that dietary calcium supplementation can have beneficial effects on adipose tissue through changes in GC and vitamin D metabolism and receptors function.…”

Anti‐obesogenic effects of calcium prevent changes in the GLP‐1 profile in adult rats primed by early weaning

“…Offspring in the C group continued to consume standard rat chow until they were 180 days old. Because a previous study found that calcium supplementation had no effect on parameters of interest in control animals , in the present study, the C group's diet was not supplemented with calcium.…”