Maternal nicotine exposure aggravates metabolic associated fatty liver disease via PI3K/Akt signaling in adult offspring mice

Abstract

Aim The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism. Methods Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11‐21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high‐fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis‐related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element‐binding transcription factor 1 (SREBP1c), and peroxisome proliferator‐activated receptor alpha (PPAR‐α) were detected in the liver by immunohistochemistry and Western blotting. Results MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low‐density lipoprotein, and insulin while decreasing serum high‐density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high‐fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down‐regulation of SREBP1c and PPAR‐α. Conclusion Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

“…After offspring rats are separated from the intrauterine high glucocorticoid environment after birth, the up-regulation of IGF1 can aggravate the lipid metabolic disorder under the condition of high-fat diet, which is the “second programming” 126 , 127 . PNE can promote the expression of phosphatidylinositol 3-kinase in offspring mouse liver, resulting in lipid metabolic disorder, insulin resistance, and NAFLD 128 , while glucocorticoids can induce phosphatidylinositol 3-kinase-related insulin resistance through GR 129 , which suggests that NAFLD in the offspring mice may be related to intrauterine overexposure to maternal-derived glucocorticoids induced by PNE. Furthermore, PNE can also induce susceptibility to hypercholesterolemia in postnatal offspring rats through “two programming”.…”

Comparison of the prognostic value of a comprehensive set of predictors in identifying risk of metabolic-associated fatty liver disease among employed adults

“…To strangle chronic liver disease in its cradle, many indicators for early detection and prevention of MAFLD have been studied. For example, anthropometric characteristics (e.g., Body Mass Index [BMI], waistline) are proposed as important factors for the development of MAFLD [ 10 ]; lifestyles (e.g., smoking [ 11 ], drinking [ 12 ], dietary pattern [ 13 ]), which are generally known modified factors for chronic disease development, were also found closely associated with MAFLD. In addition to these aforementioned factors, MAFLD is particularly determined by blood biochemical indicators.…”

Nicotine Ingestion Reduces Heart Rate Variability in Young Healthy Adults

“…Especially during pregnancy, maternal smoking is causally associated with a number of adverse pregnancy outcomes, including ectopic pregnancy, fetal growth restriction, preterm birth, placental abruption, and orofacial cleft defects [ 15 , 16 ]. In mice models, maternal nicotine exposure could significantly decrease the weight of both maternal and offspring mice (~30%), inhibit organ growth, inhibit mitochondrial respiration activity, increase the risk of fetal infection in offspring mice ( P < 0.05), and cause the development of metabolic associated fatty liver disease in adulthood offspring mice [ 17 , 18 ].…”