Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Abstract

Aim: Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods: Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results: UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion: PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.

Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats

“…Excessive GCs in fetal circulation are believed to induce abnormal fetal development (such as IUGR) and result in potential diseases in adulthood (24). Our previous studies (27,35,71) reported that PNE could induce a metabolic disorder of glucose and lipid through fetal overexposure to maternal GCs. However, it is still unclear how GCs plays its role in the programming effects of adult hypercholesterolemia.…”

“…Moreover, the suppression of fetal adrenal function could be programmed and last into adulthood (75,76), which may account for the low GC level in male adult offspring rats in this study. Meanwhile, an unconstrained hepatic IGF1 pathway promoted catch-up growth (35) and accelerated cholesterol synthesis and output by increasing the expression of related genes. Taken together, GC-IGF1 axis programming was involved in PNE-induced increased hepatic cholesterol synthesis and output and contributes to the development of hypercholesterolemia in male adult offspring rats.…”

Prenatal nicotine exposure-induced intrauterine programming alteration increases the susceptibility of high-fat diet-induced non-alcoholic simple fatty liver in female adult offspring rats

“…17 In our previous study, we confirmed that prenatal nicotine exposure might result in IUGR and maternal glucocorticoid (GC) over-exposure. 20,21 In brief, with an over-exposure to maternal GC, the development of the fetal HPA axis of the IUGR fetus was inhibited. 20,21 In brief, with an over-exposure to maternal GC, the development of the fetal HPA axis of the IUGR fetus was inhibited.…”

The brain development of infants with intrauterine growth restriction: role of glucocorticoids

“…Pregnancy stress such as pregnancy-induced hypertension, preeclampsia, malnutrition, chronic anemia and other adverse environmental stimuli lead to imbalances in the nutritional needs and supply of the fetus, resulting in IUGR, metabolism and endocrine adaptive changes [5]. These changes lead to abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) [6], [7] and subsequently in metabolism and the endocrine, behavioral and cardiovascular systems. We screened GC-related genes in IUGR rat brain tissues with the Affymetrix Rat Gene 2.0ST chip and found that the expression of glucocorticoid receptor (GR or nuclear receptor subfamily 3, group C, member 1, GR, Nr3c1) and the receptor pre-regulatory enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) were significantly higher than those of normal rats, suggesting that GCs are abnormal in IUGR rats [8], [9].…”