Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran.
Cell Mol Neurobiol. 2023 Nov;43(8):4295-4307. doi: 10.1007/s10571-023-01421-w. Epub 2023 Oct 12.
Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4-10 intervals of treadmill running at 80-100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement. Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).
2 型糖尿病（T2D）引起的瘦素（LEP）信号在下丘脑的中断会损害食欲调节。本研究旨在探讨 T2D 大鼠高强度间歇训练（HIIT）引起的食欲调节改善是否可以通过 LEP 信号介导。
在这项研究中，20 只雄性 Wister 大鼠被随机分配到以下四个组之一：CO（非 2 型糖尿病对照组）、T2D（2 型糖尿病）、EX（非 2 型糖尿病运动组）和 T2D+EX（2 型糖尿病+运动组）。为了诱导 T2D，给予高脂肪饮食 2 个月和单次链脲佐菌素（35mg/kg）注射的组合。EX 和 T2D+EX 组的大鼠在跑步机上进行 4-10 次 80-100%最大速度（Vmax）的间歇跑。稳态模型评估的胰岛素抵抗（HOMA-IR）、血清胰岛素（INS）和 LEP（LEPS）水平以及下丘脑 LEP 受体（LEP-R）、Janus 激酶 2（JAK-2）、信号转导和转录激活因子 3（STAT-3）、神经肽 Y（NPY）、刺鼠相关蛋白（AGRP）、前阿黑皮素原可卡因（POMC）、苯丙胺相关转录物（CART）、细胞因子信号转导抑制剂（SOCS3）、叉头框蛋白 O1（FOXO1）的表达进行了评估。采用方差分析和 Tukey 事后检验比较组间结果。与 T2D 组相比，T2D+EX 组的 LEPS 和 INS 水平以及 LEP-R、JAK-2、STAT-3、POMC 和 CART 水平在 T2D+EX 组中更高。另一方面，与 T2D 组相比，T2D+EX 组的 HOMA-IR、NPY、AGRP、SOCS3 和 FOXO1 水平较低（P<0.0001）。
这项研究的结果表明，HIIT 可能改善 T2D 大鼠的食欲调节，LEP 信号可能在这种改善中发挥关键作用。
