Modalities of exercise training on liver fat accretion and inflammatory markers in ovariectomized rats

Cardiovascular disease risk factors, such as lipid profile deterioration, become more pronounced after menopause making coronary heart disease a leading cause of death among postmenopausal women. A large proportion of women after menopause gain weight especially in the abdominal region resulting in several metabolic disturbances. Recent evidence also suggests that loss of estrogen function in menopause is associated with the development of a state of hepatic steatosis. Excessive fat accumulation in hepatocytes has been shown to play an important role in the development of insulin resistance and is even considered as a hepatic component of the metabolic syndrome. There is an important need to establish strategies to counteract fat accumulation in adipocyte and liver in postmenopausal women specifically considering the fact that utilization of hormone replacement therapy is now less supported. The four studies of the present thesis have been conducted in an attempt to provide information on the treatment and prevention of estrogen withdrawal-induced fat mass and hepatic steatosis via lifestyle modifications (diet and exercise training) in an ovariectomized (Ovx) rat model of menopause.  In the first two studies we focused on fat mass gain and regain following weight loss. In study 1, we showed that food restriction program (FR) decreased (P < 0.01) body mass, intra-abdominal fat pad weight, and liver triacylglycerol (TAG) levels as compared to normally fed Ovx rats. Moreover, resistance training program (RT) was useful in preventing body weight as well as adipose tissue and liver fat regain in Ovx rats, following diet-induced weight loss. Results of study 2 confirmed the efficiency of the FR + RT program in reducing body weight as well as liver and adipocytes fat accretion in Ovx rats. In line with the findings of our first study, continuation of only RT constituted an asset to attenuate body weight and fat mass regain in Ovx rats following a FR + RT weight loss program, although the impact was less than maintaining FR alone. Similar to estrogen supplementation, results of study 3 indicated that endurance exercise training conducted concurrently with the induction of ovariectomy significantly attenuated liver and adipocyte fat accumulation. However, an endurance exercise training state acquired before ovariectomy did not provide any protective effects against ovariectomy-induced fat accumulation if exercise is discontinued after the ovariectomy. Finally, complementing previous findings we showed in study 4 that liver gene expressions of transcription factors SREBP-1c and ChREBP along with downstream lipogenic enzymes SCD-1 and ACC were increased with estrogens withdrawal conversely to reduced PPAR-α mRNA levels (P < 0.01). Furthermore, gene expressions of pro-inflammatory cytokines including IKKβ and IL-6 as well as protein content of NF-кB were higher (P < 0.01) in the liver of Ovx than in Sham animals. All of these responses were corrected with estrogen supplementation alone as well as with endurance exercise training alone in Ovx rats.  On the whole, our results indicate that exercise training (resistance or endurance) has a significant impact on reducing fat accumulation in liver and adipocytes in Ovx rats. In addition, it seems that endurance exercise training in Ovx rats stimulates estrogenic-like effects on the expression of genes involved in lipid accumulation and sub-clinical inflammation in the liver.

Keyphrases: Foie gras, Ovariectomie (Ovx), Rat, Estrogen, Menopausal obesity, Weight and fat regain, Hepatic steatosis, Food restriction, Resistance training, Endurance exercise training, Inflammatory bio-markers, Ovariectomy (Ovx), Rat