Sardinha Fátima L C, Telles Mônica M, Albuquerque Kelse T, Oyama Lila M, Guimarães Paulo A M P, Santos Oscar F P, Ribeiro Eliane B
Department of Physiology, Division of Nutrition Physiology, Federal University of São Paulo-UNIFESP, São Paulo, Brazil.
Nutrition. 2006 Nov-Dec;22(11-12):1152-61. doi: 10.1016/j.nut.2006.07.002. Epub 2006 Oct 9.
We evaluated whether insulin hypophagia and hypothalamic signaling are affected in adult rats exposed to intrauterine undernutrition.
Pregnant rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C and R progeny received insulin or vehicle intracerebroventricular injections for evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185 phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3-K).
With respect to males, R males had normal body composition and insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation was higher in R than in C males. IRS-1 levels and phosphorylation were similar between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not in R males, and pp185 phosphorylation was higher in R than in C males. For females, body fat and serum leptin were elevated in R females. Insulin inhibited food intake in C but not in R females. Insulin-induced IR phosphorylation and protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1 and pp185 phosphorylation and IRS-1/PI3-K association were significantly stimulated by insulin in C but not in R females.
Female adult rats exposed to intrauterine undernutrition had increased adiposity, marked impairment of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These disturbances were less severe or even absent in male progeny. The findings show that female progeny are more susceptible than their male siblings to the effects of maternal malnutrition.
我们评估了暴露于子宫内营养不良的成年大鼠的胰岛素性摄食减少及下丘脑信号传导是否受到影响。
怀孕大鼠在整个孕期和哺乳期自由进食（对照组，C），或在怀孕的前2周摄入对照组摄入量的50%（限制组，R）。对4月龄的C组和R组后代进行脑室内注射胰岛素或赋形剂，以评估24小时食物摄入量、下丘脑胰岛素受体（IR）、胰岛素受体底物-1（IRS-1）蛋白含量及酪氨酸磷酸化、pp185磷酸化以及IRS-1与磷脂酰肌醇3激酶（PI3-K）的结合情况。
对于雄性大鼠，R组雄性大鼠的身体组成和胰岛素诱导的摄食减少正常。R组雄性大鼠的IR蛋白水平低于C组，但IR磷酸化水平高于C组。C组和R组雄性大鼠的IRS-1水平及磷酸化水平相似，胰岛素刺激C组雄性大鼠的IRS-1/PI3-K结合，但不刺激R组雄性大鼠，且R组雄性大鼠的pp185磷酸化水平高于C组。对于雌性大鼠，R组雌性大鼠的体脂和血清瘦素升高。胰岛素抑制C组雌性大鼠的食物摄入，但不抑制R组雌性大鼠。胰岛素诱导的IR磷酸化以及IR和IRS-1的蛋白水平在R组雌性大鼠中高于C组。然而，胰岛素显著刺激C组雌性大鼠的IRS-1和pp185磷酸化以及IRS-1/PI3-K结合，但不刺激R组雌性大鼠。
暴露于子宫内营养不良的成年雌性大鼠肥胖增加、下丘脑胰岛素信号传导明显受损且胰岛素诱导的摄食减少消失。这些紊乱在雄性后代中不太严重甚至不存在。研究结果表明，雌性后代比其雄性同胞对母体营养不良的影响更敏感。
