Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats

Abstract

Smoking during pregnancy is one of the causes of low birthweight. Ingestion of nicotine during pregnancy has various metabolic impacts on the fetus and offspring. According to the developmental origins of health and disease theory, low birthweight is a risk factor for developing various non-communicable diseases, including diabetes. We hypothesized that when nicotine-induced low-birthweight rats, when exposed to a high-fat diet (HFD) after growth, are predisposed to glucose intolerance as a result of a mismatch between the eutrophic environment and small body size. Therefore, we investigated whether hyperinsulinemia was caused by exposure of nicotine-induced low-birthweight rats to HFD, including whether this phenomenon exhibited possible sex differences. The average birthweight and body weight at weaning day of offspring from nicotine-administered dams was lower than those of controls. The offspring from nicotine-administered dams did not show rapid fat accumulation after exposure to HFD, and weight and body fat ratio of these animals did not differ from those of the controls. Blood glucose levels did not differ between the groups, but insulin levels increased only in male HFD-exposed offspring from nicotine-administered dams. Similarly, only in HFD-exposed male from nicotine-administered dams showed decreases in the insulin receptor expression in the liver. We conclude that male rats subjected to prenatal nicotine exposure develop hyperinsulinemia when exposed to HFD after growth. Our results suggest that decreased expression of insulin receptors in the liver may be involved in the mechanism underlying hyperinsulinemia in low-birthweight offspring, a phenomenon that appeared to exhibit a sex-specific bias.

Analysis of Maternal Predisposing Factors with The Incidence of LBW in Central Java

“…There were no relationships between the quality of ANC, iron supplementation, and maternal smoking status with the incidence of LBW in Central Java (Table 1). (Nemoto et al, 2021). The incidence of LBW in Taiwan was associated with maternal smoking status (OR = 3.46) (Ko et al, 2014).…”

Prevention of transgenerational transmission of disease susceptibility through perinatal intervention

“…Prenatal nicotine exposure caused a decrease in blood IGF-1 levels, similar to prenatal undernutrition, but it is thought that the mechanism is not mediated by miR-322 and GHR, but by some other mechanism. However, LBW model rats exposed to nicotine during the prenatal period also showed elevated blood insulin levels when exposed to a high-fat diet [77]. In other words, LBW, albeit from different causes, has been proven to predispose to the risk of NCDs.…”

“…Small body size rats with LBW and NCG showed increased miR-322 expression and decreased GH receptor expression in the liver, and reduced blood IGF-1 levels. It was shown that the gene was transgenerationally inherited to at least the F4 generation [77]. However, the DNA methylation of miR-322 seen in the F1 generation was not recapitulated in the F2 and later generations, and the mechanism of miR-322 upregulation remains unclear.…”

Xenobiotics Delivered by Electronic Nicotine Delivery Systems: Potential Cellular and Molecular Mechanisms on the Pathogenesis of Chronic Kidney Disease

“…Nicotine is the tobacco compound most highly correlated with metabolic dysfunction in offspring of tobacco addict mothers. Exposure of pregnant mice to nicotine caused several systemic effects in the mother and offspring, including insulin resistance [ 98 , 99 , 100 ]. Robust investigations support that nicotine intake leads to glucocorticoid overexposure in the mother.…”

“…It promotes post-translational histones in perivascular adipose tissue and β-cells [ 102 , 103 ]. Recently, it was found that a pre-diabetic state in offspring of nicotine-exposed dams was associated with downregulated transcription factor sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-α (PPAR-α), and insulin receptor in the liver [ 99 , 104 ]. SREBP-1c transduces the insulin signal and induces the expression of a family of genes involved in glucose utilization, fatty acid synthesis, and PPAR-α regulates glucose synthesis during fasting states and gluconeogenesis [ 105 ].…”