Maternal Nicotine Exposure Leads to Augmented Expression of the Antioxidant Adipose Tissue Triglyceride Lipase Long-Term in the White Adipose of Female Rat Offspring

Abstract

Globally, approximately 10%-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine-containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (eg, lipid storage) underlie dyslipidemia in MNE adults. Female 6-month-old rats exposed to nicotine during gestation and lactation exhibited significantly decreased visceral adipocyte cell area by 40%, attributed, in part, to a 3-fold increase in adipose triglyceride lipase (ATGL) protein expression compared with vehicle. Given ATGL has antioxidant properties and in utero nicotine exposure promotes oxidative stress in various tissues, we next investigated if there was evidence of increased oxidative stress in MNE WAT. At both 3 weeks and 6 months, MNE offspring expressed 37%-48% higher protein levels of superoxide dismutase-1 and -2 in WAT. Since oxidative stress can induce inflammation, we examined the inflammatory profile of WAT and found increased expression of cytokines (interleukin-1β, tumor necrosis factor α, and interleukin-6) by 44%-61% at 6 months. Collectively, this suggests that the expression of WAT ATGL may be induced to counter MNE-induced oxidative stress and inflammation. However, higher levels of ATGL would further promote lipolysis in WAT, culminating in impaired lipid storage and long-term dyslipidemia.

Investigating Behavioral and Neuronal Changes in Adolescent Mice Following Prenatal Exposure to Electronic Cigarette (E-Cigarette) Vapor Containing Nicotine

“…The recorded weight gain indicated that the 2.5%-nicotine-exposed group exhibited the most significant gain in body weight from the beginning to the end of adolescence. Accumulating evidence has linked prenatal nicotine exposure and obesity later in life [33][34][35]. Clinical settings have revealed that prenatal exposure to traditional nicotine is associated with increased weight gain during adolescence, including subcutaneous and intra-abdominal fat [36].…”

The Role of Cellular Stress in Intrauterine Growth Restriction and Postnatal Dysmetabolism

“…Interestingly, protein-restricted rat offspring show increased antioxidant abundance in skeletal muscle, concomitant with altered activity of aerobic metabolism enzymes [62]. Gestational exposure to nicotine has been found to elicit similar effects in adipose tissue at three weeks and six months of age, as SOD1 and SOD2 protein levels were 37-48% higher in the white adipose tissue of IUGR offspring compared to control offspring [63]. While the increase in antioxidant abundance is thought to occur as a compensatory mechanism in response to oxidative stress, it has also been proposed that inflammation may have a contributing role in this process [62,63].…”

The Role of Cellular Stress in Intrauterine Growth Restriction and Postnatal Dysmetabolism

“…Interestingly, protein-restricted rat offspring show increased antioxidant abundance in skeletal muscle, concomitant with altered activity of aerobic metabolism enzymes [63]. Gestational exposure to nicotine has been found to elicit similar effects in adipose tissue at three weeks and six months of age, as SOD1 and SOD2 protein levels were 37-48% higher in the white adipose tissue of IUGR offspring compared to control offspring [64]. While the increase in antioxidant abundance is thought to occur as a compensatory mechanism in response to oxidative stress, it has also been proposed that inflammation may have a contributing role in this process [63,64].…”