Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver

Abstract 

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.