Peixoto T C, Moura E G, Oliveira E, Younes-Rapozo V, Soares P N, Rodrigues V S T, Santos T R, Peixoto-Silva N, Carvalho J C, Calvino C, Conceição E P S, Guarda D S, Claudio-Neto S, Manhães A C, Lisboa P C
Laboratório de Fisiologia Endócrina, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Laboratório de Neurofisiologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Braz J Med Biol Res. 2018;51(6):e6982. doi: 10.1590/1414-431x20186982. Epub 2018 Apr 19.
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.
母亲吸烟是后代肥胖的一个风险因素。我们之前在新生大鼠烟草烟雾暴露模型中发现,成年后代的食物摄入量略有增加,内脏脂肪明显增多。雄性后代还出现继发性甲状腺功能亢进,而雌性后代仅T4水平较高。由于棕色脂肪组织(BAT)功能减退与肥胖有关,因此我们在此测试了以下假设:较高水平的甲状腺激素在BAT中不起作用,这表明代谢率较低。我们评估了哺乳期暴露于烟草烟雾的成年大鼠BAT中的自主神经活动及其功能。出生时,将每窝幼崽调整为3只雄性和3只雌性幼崽。从出生后第3天(PND)到第21天,将Wistar哺乳期大鼠及其幼崽分为SE组,在吸烟机中暴露于烟雾(每天4次)和C组,暴露于过滤空气中。在PND180处死后代。两种性别的成年SE大鼠肩胛间BAT自主神经系统活动均较低,BAT质量较高,但形态无变化。两种性别的SE组中BAT的解偶联蛋白1(UCP1)和肉碱棕榈酰转移酶1a(CPT1a)蛋白水平均降低。雄性SE大鼠的β3-肾上腺素能受体(β3-AR)、甲状腺激素受体α1(TRα1)和甲状腺激素受体β1(TRβ1)表达较低,而雌性大鼠的过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC1α)表达较低。两组之间BAT脱碘酶2(Dio2)mRNA以及下丘脑阿黑皮素原(POMC)和黑皮质素4受体(MC4R)水平相似。SE雄性大鼠下丘脑磷酸化腺苷酸活化蛋白激酶(pAMPK)水平较高,SE雌性大鼠较低。因此,新生儿暴露于香烟烟雾会导致BAT产热能力降低,这在成年期可能会导致肥胖。