Biosciences Department, Institute of Health and Society, Federal University of São Paulo, Campus Baixada Santista - UNIFESP/BS, Santos, São Paulo, 11015-020, Brazil.
Pflugers Arch. 2021 Aug;473(8):1199-1211. doi: 10.1007/s00424-021-02583-6. Epub 2021 Jun 1.
Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. The obesity propensity is more associated with energy intake than expenditure dysregulations and may have a link with AMPK activity. While the effects of ODs are studied widely, few evaluate the short-term effects of terminating OD intake. Withdrawing from OD (WTD) is thought to improve or reverse the damages caused by the intake. Therefore, here we applied an OD intake and WTD protocol aiming to evaluate AMPK protein content and phosphorylation in the colon, liver, and hypothalamus and their relationship with obesity propensity. To this end, male Wistar rats (60 days) received control or high-sugar/high-fat (HSHF) OD for 30 days. Half of the animals were OD-withdrawn and fed the control diet for 48 h. After intake, we found a reduction in AMPK phosphorylation in the hypothalamus and colon, and after WTD, we found an increase in its hepatic and hypothalamic phosphorylation. The decrease in colon pAMPK/AMPK could be linked with hypothalamic pAMPK/AMPK after HSHF intake, while the increase in hepatic pAMPK/AMPK could have prevented the increase in hypothalamic pAMPK/AMPK. In the obesity-prone rats, we found higher levels of hypothalamic and colon pAMPK/AMPK despite the higher body mass gain. Our results highlight the relevance in multi-organ investigations and animal phenotype evaluation when studying the energy metabolism regulations.
致肥饮食（ODs）可影响 AMPK 在多个部位的激活，如结肠、肝脏和下丘脑。OD 的摄入会损害下丘脑对能量平衡的 AMPK 调节。尽管摄入了致肥饮食，但并非所有受试者都有发展或进展为肥胖的倾向。肥胖倾向与能量摄入的紊乱比支出更为相关，并且可能与 AMPK 活性有关。虽然广泛研究了致肥饮食的影响，但很少有研究评估终止致肥饮食摄入的短期影响。退出致肥饮食（WTD）被认为可以改善或逆转摄入所造成的损害。因此，我们在这里应用了一种致肥饮食摄入和 WTD 方案，旨在评估 AMPK 蛋白含量和磷酸化在结肠、肝脏和下丘脑的表达，并研究其与肥胖倾向的关系。为此，雄性 Wistar 大鼠（60 天）接受对照或高糖/高脂肪（HSHF）致肥饮食 30 天。一半的动物进行致肥饮食摄入和 WTD，并在 48 小时内喂食对照饮食。摄入后，我们发现下丘脑和结肠的 AMPK 磷酸化减少，WTD 后，发现其肝脏和下丘脑的磷酸化增加。HSHF 摄入后，结肠 pAMPK/AMPK 的减少可能与下丘脑 pAMPK/AMPK 有关，而肝 pAMPK/AMPK 的增加可能防止了下丘脑 pAMPK/AMPK 的增加。在肥胖倾向大鼠中，尽管体重增加较高，我们仍发现了更高水平的下丘脑和结肠 pAMPK/AMPK。我们的结果强调了在研究能量代谢调节时，多器官研究和动物表型评估的相关性。
