Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

Abstract

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

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

“…Whilst there was increased fat mass and unchanged fatty acid metabolic marker Cpt1α, plasma TG was not affected by maternal programming nor postnatal HFD consumption, which might be due to the mouse strain specific. It has previously been shown that with cigarette SE only during lactation, there were decreased proteins levels of Ucp1 and Cpt1 and reduced sympathetic nerve stimulation upon BAT in female adult rat ( 55 ). The same was observed with the administration of isolated nicotine through minipumps on the dams at the same period ( 56 ).…”

Effects of Exposure to Tobacco Cigarette, Electronic Cigarette and Heated Tobacco Product on Adipocyte Survival and Differentiation In Vitro

“…In contrast, the extent of nicotine-or cigarette smoke-elicited effects on brown or "beige" adipocytes are still very limited. In this respect, recent research has shown that neonatal CS exposure evoked decreased thermogenic capacity of brown fat at an adult age [38]. Nicotine treatment of 3T3-L1 pre-adipocytes exhibited a complex effect depending on which stage of differentiation towards beige adipocytes occurred the exposure; at the early differentiation stage, the beige-like phenotype was impaired, whereas it was enhanced when nicotine was administered only at the later, "maintenance" stage or during the entire differentiation process [39].…”

Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications

“…The food restriction during pregnancy is the most common maternal stress ( Smart and Dobbing, 1971 ; Hales and Barker, 1992 ; Roseboom et al, 2001 ). However, obesity, diabetes ( Armitage et al, 2008 ; Shankar et al, 2008 ; Agarwal et al, 2018 ), stressful life events, air pollution ( Burris and Baccarelli, 2017 ; Almeida et al, 2019 ; Wang et al, 2020 ), nicotine/tobacco smoke ( Butler and Goldstein, 1973 ; Khorram et al, 2010 ; Santos-Silva et al, 2013 ; Younes-Rapozo et al, 2013 ; Lisboa et al, 2017 ; Peixoto et al, 2018 ), and the use of synthetic glucocorticoids ( Guo et al, 2020 ; Li et al, 2020 ; Arias et al, 2021 ) are important factors influencing the offspring health in later life, since they disrupt maternal and offspring physiology. Although stress induces different signaling pathways, the glucocorticoids are key mediators of stress response ( Molnar et al, 2003 ; Moisiadis and Matthews, 2014a ; Facchi et al, 2020 ) and beside their important role in the acute stress condition, glucocorticoids can also chronically affect the offspring brain neuronal connectivity, stability, and maturation, which can modulate hypothalamic energy controlling pathways ( Arck et al, 2001 ; Sandman et al, 2011 ; Christian et al, 2013 ; Solano et al, 2016 ; Osborne et al, 2018 ; Schepanski et al, 2018 ; Nazzari et al, 2020 ; Figure 1 ).…”