Clarification of the molecular mechanism(s) behind exercise training-induced suppression of fat mass

为了阐明运动或运动训练诱导的脂肪量抑制背后的机制，在大鼠脂肪细胞中进行了以下研究：（1）运动对细胞凋亡和抗凋亡信号的影响;（2）运动和饮食对几个与脂代谢相关的基因的影响;（3）运动对肿瘤坏死因子-α（TNF-α）诱导的细胞凋亡和抗凋亡信号的影响;（4）运动训练对胰岛分泌胰岛素的影响;（5）运动诱导的β-肾上腺素能受体和G蛋白的变化。结果，获得了以下发现。运动使腹膜后和腹股沟脂肪组织中Bcl 2/Bax比值升高，而使附睾脂肪组织中Bcl 2/Bax比值降低。饥饿降低了某些脂肪生成基因的表达，而再喂养增强了这些基因的表达。再喂食后运动可阻断再喂食诱导的某些脂肪生成基因表达的增强。运动训练增强了TNF-α信号传导，直接指向生存信号的表达和脂肪酸合成酶基因表达的抑制。运动训练导致胰岛素分泌减少的机制可能与神经元型一氧化氮合酶表达增加和Gαi-2蛋白表达减少有关。急性运动通过泛素-蛋白酶体途径改变Giα2蛋白的表达，运动后β 2-AR密度增加的机制可能涉及一个多步骤事件的改变，涉及介导β 2-AR运输的蛋白质之间的协调相互作用，如G蛋白偶联受体激酶2和β-arrestin 2。因此，本研究获得的数据将有助于更准确地了解运动训练诱导的脂肪量抑制机制。

In order to clarify the mechanism(s) behind either exercise- or exercise training-induced suppression of fat mass, the following studies were performed in rat adipocytes : (1)effects of exercise on apoptotic and anti-apoptotic signals, (2)effects of exercise and diet on several genes related with lipid metabolism, (3)effects of exercise on tumor necrosis factor-α (TNF-α)-induced apoptotic and anti-apoptotic signals, (4)effect of exercise training on insulin secretion from pancreatic islets, (5)alterations in exercise-induced β-adrenergic receptors and G proteins. As a result, the following findings were obtained. Exercise increased the Bcl2/Bax ratio in retroperitoneal and inguinal adipose tissue, but decreased its ratio in epididymal adipose tissue. Starvation reduced the expressions of some lipogenic genes, and re-feeding enhanced these expressions. Exercise after re-feeding blocked re-feeding-induced enhancement of some lipogenic genes expressions. Exercise training enhanced TNF-α signaling directed toward the expressions of survival signals and the suppression of fatty acid synthase gene expression. The mechanism behind exercise training-induced reduction of insulin secretion may involve an enhanced expression of neuronal nitric oxide synthase and a decreased expression of Gαi-2 protein. Acute exercise altered the expression of Giα2 protein via the ubiquitin-proteasome pathway, and the mechanism underlying the increased density of β_2-AR after exercise may involve alterations in a multi-step event involving the coordinate interaction among proteins mediating β_2-AR trafficking, e.g. G-protein-coupled receptor kinase-2 and β-arrestin-2. Thus, the data obtained in this grant will become helpful to understand more exact mechanism behind exercise training-induced suppression of fat mass.