Department of Kinesiology, Université de Montréal, Montreal, Quebec, Canada.
Metabolism. 2011 May;60(5):629-39. doi: 10.1016/j.metabol.2010.06.012. Epub 2010 Aug 2.
We hypothesized that the reduction in liver fat accumulation known to occur with exercise training in ovariectomized (Ovx) rats is associated with reduced expression of genes involved in lipogenesis while favoring the expression of transcription factors regulating lipid oxidation. We also tested the hypothesis that liver fat accumulation in Ovx rats is associated with an increased gene expression of several inflammatory biomarkers and that exercise training would attenuate this response. Sprague-Dawley female rats (14 weeks of age) were randomly divided into 4 groups of sedentary sham-operated (Sham), Ovx, Ovx with 17β-estradiol (E2) supplementation using a pellet (0.72 mg; 0.012 mg/d) with a biodegradable carrier binder, and Ovx trained with endurance exercise. Endurance exercise training consisted of continuous running on a motor-driven rodent treadmill 5 times per week for 5 weeks. Fat accumulation in liver as well as in adipose fat depots was higher (P < .01) in Ovx than in Sham rats. This response was prevented in Ovx animals with 17β-estradiol supplementation and with endurance exercise training. Liver gene expressions of sterol regulatory element-binding protein 1-c, stearoyl coenzyme A desaturase 1 (and its protein content), carbohydrate response element binding protein, and acetyl-coenzyme A carboxylase were increased with estrogen withdrawal (P < .01). These responses were corrected with E2 supplementation alone as well as with training alone. Conversely, hepatic peroxisome proliferator-activated receptor α messenger RNA levels were lower (P < .01) after estrogen removal compared with Sham rats. The lower hepatic peroxisome proliferator-activated receptor α messenger RNA levels in Ovx rats were reincreased by E2 replacement or by exercise training. Gene expression of proinflammatory cytokines including inhibitor-κB kinase β and interleukin-6, as well as protein content of nuclear factor-κB, was higher (P < .01) in Ovx than in Sham animals. E2 supplementation or exercise training prevented the expression of the proinflammatory markers. It is concluded that exercise training reduces fat accumulation in liver of Ovx rats possibly through regulation of key molecules involved in lipogenesis and lipid oxidation. Exercise training also acts as estrogens in properly regulating the expression of inflammatory biomarkers in liver of Ovx rats.
我们假设，在去卵巢（Ovx）大鼠中，运动训练导致的肝脂肪积累减少与参与脂肪生成的基因表达减少有关，同时有利于调节脂质氧化的转录因子的表达。我们还测试了以下假设，即 Ovx 大鼠的肝脂肪积累与几种炎症生物标志物的基因表达增加有关，并且运动训练会减弱这种反应。14 周龄的 Sprague-Dawley 雌性大鼠被随机分为 4 组：久坐假手术（Sham）组、Ovx 组、用具有生物降解载体结合剂的丸剂（0.72 mg；0.012 mg/d）补充 17β-雌二醇（E2）的 Ovx 组和进行耐力运动训练的 Ovx 组。耐力运动训练包括每周 5 次连续在电动啮齿动物跑步机上跑步，持续 5 周。Ovx 大鼠的肝脏和脂肪组织中的脂肪积累高于（P <.01）Sham 大鼠。这种反应在用 17β-雌二醇补充和耐力运动训练的 Ovx 动物中得到了预防。肝脏固醇调节元件结合蛋白 1-c、硬脂酰辅酶 A 去饱和酶 1（及其蛋白含量）、碳水化合物反应元件结合蛋白和乙酰辅酶 A 羧化酶的基因表达随着雌激素的撤出而增加（P <.01）。这些反应仅用 E2 补充或仅用训练即可纠正。相反，与 Sham 大鼠相比，肝过氧化物酶体增殖物激活受体 α 信使 RNA 水平在雌激素去除后降低（P <.01）。Ovx 大鼠的肝过氧化物酶体增殖物激活受体 α 信使 RNA 水平较低，通过 E2 替代或运动训练可重新升高。包括抑制剂-κB 激酶 β 和白细胞介素 6 在内的促炎细胞因子的基因表达以及核因子-κB 的蛋白含量在 Ovx 动物中高于（P <.01）Sham 动物。E2 补充或运动训练可防止促炎标志物的表达。结论是，运动训练可能通过调节参与脂肪生成和脂质氧化的关键分子来减少 Ovx 大鼠肝脏的脂肪积累。运动训练还可以作为雌激素，在适当调节 Ovx 大鼠肝脏中炎症生物标志物的表达方面发挥作用。
Zotero 插件