Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition

Abstract

Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.

L-Leucine Improves Metabolic Disorders in Mice With in-utero Cigarette Smoke Exposure

“…Previously, leucine supplement was shown to improve glucose metabolic disorders due to maternal obesity in male offspring (Chen et al, 2012;Saad et al, 2018). As this study was only performed on female mice, the positive outcome on glucose metabolism may not happen in the male offspring, who also showed similar metabolic disorders in our previous studies on the same model (Nguyen et al, 2015;Saad et al, 2018;Li et al, 2019;Huang et al, 2021). Future studies can investigate a dose-response curve of such treatment in both male and female offspring.…”

“…After acclimatization, mice with similar body weight were randomly assigned to two groups, sham exposure (SHAM) and SE. The SE group was exposed to smoke produced by 2 cigarettes (Double Happiness; Tar: 8 mg; nicotine: 0.7 mg; CO: 12 mg) inside a perspex box (18 liters) in the fume hood, twice a day for 5 weeks before mating and during the gestation and lactation periods following a published protocol as we have previously published (Huang et al, 2021 ). The breeders in the SHAM group were treated identically except for the exposure to the air.…”

“…Therefore, we hypothesized that in offspring from dams exposed to cigarette smoke during pregnancy, postnatal L-leucine supplement in drinking water will prevent excess fat accumulation and benefit glycemic control in adulthood. To address this hypothesis, we used our published mouse model of maternal SE (Huang et al, 2021 ) and supplied L-leucine in the drinking water to the female offspring from weaning for 10 weeks until they reached adulthood. As there is no sexual difference in metabolic disorders due to maternal SE, we only studied females.…”

Nutrition and Developmental Origins of Kidney Disease

“…Such an example demonstrates the complexity in metabolic programming, which contributes to the varied susceptibility to CKD development later in life. As maternal smoking is known to induce FGR, its combination with maternal obesity was shown to exacerbate adiposity and metabolic disorders in male offspring [71], which further predispose them to CKD.…”