Roles of adiponectin and leptin signaling-related microRNAs in the preventive effects of calorie restriction in mammary tumor development.

Calorie restriction (CR) is suggested to prevent the development of mammary tumors (MTs); however, the mechanism remains to be clarified. We aimed to determine the microRNA (miRNA) profile in mice applied to 2 different CR protocols; chronic (CCR) and intermittent (ICR) and follow the MT development. In addition, the roles of miRNAs involved in adiponectin and/or leptin signaling pathways were investigated. Mice were divided into 3 groups: ad-libitum (AL), CCR, or ICR, which comprised 3 weeks of AL feeding followed by 1 week of 60% CR in a cyclic manner. Blood and tissue collection were performed at weeks 10, 17/18, 49/50 and 81/82. Long-term CCR provided better protection compared with ICR for MT development with a delay in the MT occurrence. Adiponectin expression in mammary fat pad were significantly higher in CCR group compared with AL. Using GeneChip Array, 250 of 3195 miRNAs were differentially expressed among the dietary groups. Thirteen of 250 miRNAs were related to adiponectin and/or leptin signaling genes. Results were verified by reverse transcription polymerase chain reaction. Specifically, miR-326-3p, miR-500-3p and miR-129-5p, which are related to adiponectin and/or leptin signaling, may play important roles in the preventive effects of CR in MT development and in ageing. Thus, these miRNAs might be putative biomarkers to target for diagnostic and treatment purposes. Novelty: Type of CR and micro RNA interaction is related to ageing. miR-326-3p, miR-500-3p and miR-129-5p expression levels were differentially expressed in MT development and in ageing. The genes associated with adiponectin and/or leptin signaling pathways are regulated by certain miRNAs in the protective effects of CR.

Effects of hormone replacement therapy on plasma and tissue fibrinolytic activity in a rat model of surgically induced menopause.

PURPOSE: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. METHODS: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200-250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17ß-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17ß-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. RESULTS: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. CONCLUSIONS: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.