School of Applied Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
FEBS Open Bio. 2013 Sep 11;3:443-9. doi: 10.1016/j.fob.2013.09.002. eCollection 2013.
Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala.
胰岛素在下丘脑发挥作用，通过胰岛素受体（IR）/磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）通路减少食物摄入（FI）。在肥胖动物中，该通路受损，内质网（ER）应激和低度炎症可能是导致这种损伤的机制。在这里，我们强调了杏仁核作为响应胰岛素调节 FI 的重要脑区。这种调节依赖于 PI3K/Akt 通路，与下丘脑相似。胰岛素通过 PI3K 降低杏仁核中神经肽 Y（NPY）和增加催产素 mRNA 水平，这可能有助于减少摄食。此外，肥胖大鼠对胰岛素没有减少 FI，并且 AKT 磷酸化在杏仁核中减少，表明胰岛素抵抗。在该脑区，胰岛素抵抗与 ER 应激和低度炎症有关。用 PBA 抑制 ER 应激可逆转肥胖大鼠杏仁核中的胰岛素作用/信号，降低 NPY 并增加催产素 mRNA 水平，表明 ER 应激可能是诱导杏仁核胰岛素抵抗的机制之一。
