Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J Endocrinol. 2010 Jul;206(1):55-63. doi: 10.1677/JOE-10-0104. Epub 2010 May 7.
Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.
哺乳期母体尼古丁（NIC）暴露会导致成年大鼠后代超重、高瘦素血症和甲状腺功能减退。在该模型中，我们分析了脂肪细胞形态、葡萄糖稳态（血清胰岛素和脂联素；肝和肌肉糖原）、血清脂质和瘦素信号通路。出生后，将渗透微型泵植入哺乳期大鼠体内，将其分为 NIC 组（每天皮下注射 6mg/kg，共 14 天）和对照组（C，生理盐水）。NIC 和 C 组后代在 180 天大时被处死。成年 NIC 大鼠表现出更高的总体脂肪量（+10%，P<0.05）、内脏脂肪质量（+12%，P<0.05）和脂肪细胞的横截面积（附睾：+12%和腹股沟：+43%，P<0.05）。血清脂质谱除载脂蛋白 AI 降低外无其他改变。我们检测到较低的脂联素：脂肪量比值（-24%，P<0.05）和较高的血糖（+56%，P<0.05）、胰岛素抵抗指数（+43%，P<0.05）、瘦素血症（+113%，P<0.05）和瘦素：脂联素比值（+98%，P<0.05）在成年 NIC 组。这些大鼠下丘脑瘦素信号通路蛋白含量降低（瘦素受体（OB-R）：-61%，Janus 酪氨酸激酶 2：-41%，信号转导和转录激活因子 3：-56%，P<0.05），但抑制细胞因子信号转导 3 增加（+81%，P<0.05）。因此，哺乳期仅暴露于 NIC 会导致成年大鼠脂肪细胞肥大，并导致瘦素和胰岛素抵抗。通过 NIC 的作用，围产期母亲吸烟可能导致后代代谢综合征的某些成分的未来发展。
