Synergistic effects of prenatal nicotine exposure and post‐weaning high‐fat diet on hypercholesterolaemia in rat offspring of different sexes

Abstract

Hypercholesterolaemia is considered a disease with intrauterine origin. Recently, we reported that prenatal nicotine exposure (PNE) induced an abnormal level of total cholesterol in rat offspring before and after birth. However, there were little data about sex differences in serum cholesterol level in PNE offspring. In addition, many previous studies reported that blood cholesterol is associated with daily diet. This study was designed to analyse the interaction among PNE, high-fat diet (HFD) and sex on cholesterol metabolism in the rat. Pregnant Wistar rats were administered 2 mg/kg nicotine subcutaneously from gestational day (GD) 11 until parturition. After weaning, pups were fed with normal diet or HFD till 24 weeks, and then, serum cholesterol phenotypes and hepatic cholesterol metabolism-related genes were tested. Results showed that PNE manifested a distinct programming effect on cholesterol phenotype and cholesterol metabolism-related genes. HFD aggregated PNE-induced hypercholesterolaemia in adult offspring and exacerbated liver cholesterol metabolism dysfunction in PNE offspring. There was no sex difference in serum cholesterol level, but there were interactions among PNE, HFD and sex on cholesterol metabolic genes in adult offspring, which indicates that cholesterol metabolism in female offspring is more likely to be affected by PNE and HFD. In conclusion, HFD exacerbated PNE-induced hypercholesterolaemia, and sex differences existed in liver cholesterol metabolic genes in PNE-or HFDtreated offspring. K E Y W O R D Shigh-fat diet, hypercholesterolemia, liver cholesterol metabolism, pregnancy nicotine exposure, sex

Comparison of Protective Effects of Electroacupuncture at ST 36 and LU 5 on Pulmonary and Hypothalamic Pituitary Adrenal Axis Changes in Perinatal Nicotine-Exposed Rats

“…According to the World Health Organization, more than 1 billion people around the world smoke, and 5 million die from cigarettes each year. In China, the current smoking rate for adults, aged 15 and over, is 27.7, percent and the total number of smokers is more than 300 million (China Adult Tobacco Survey, 2015). Even though the rate of active smoking during pregnancy in China is relatively low, the exposure rate to secondhand smoke during pregnancy is alarmingly high (>50%) [1].…”

“…Nicotine levels in the amniotic fluid can exceed maternal plasma levels by 88% [8,9]. Perinatal nicotine exposure is harmful to the health of the offspring in many aspects; it results in low birth weight, preterm delivery, stillbirth, neurobehavioral deficits, sudden infant death syndrome, and a range of neuroendocrine, craniofacial, and immune system abnormalities [10][11][12][13][14][15][16]. In addition to these problems, it is especially harmful to the developing respiratory system.…”

Loss of the Protective Effect of Estrogen Contributes to Maternal Gestational Hypertension‐Induced Hypertensive Response Sensitization Elicited by Postweaning High‐Fat Diet in Female Offspring

“…It has been shown that perinatal programmed offspring can be affected by a “second hit,” such as HFD that exacerbates their cardiometabolic health in a sex‐specific manner. 18 , 19 , 20 , 21 , 22 , 23 In these studies, the researchers focused on peripheral mechanisms, such as renal function, glucose homeostatic response, and systemic and adipose renin‐angiotensin system (RAS), that are involved in the sex differences in cardiometabolic dysfunction in offspring with both prenatal insult and postnatal HFD feeding. Although a large body of studies have shown central interactions between sex hormones and the RAS, proinflammatory cytokines (PICs), and leptin influencing SNS activity and BP, 15 , 24 , 25 , 26 , 27 , 28 , 29 the mechanisms underlying central regulatory effects of sex hormones, especially estrogen regulation of autonomic function in HFD fed offspring of maternal hypertensive dams, have not been explored.…”