Roles of Adiponectin and Leptin Signaling Related microRNAs in The Preventive Effects of Calorie Restriction in Mammary Tumor Development

Calorie restriction (CR) is suggested preventing development of mammary tumors (MT) however the mechanism remains to be clarified. We aimed to determine the miRNA profile in mice applied to two 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 enrolled into ad-libitum (AL), CCR, or ICR which was three-weeks AL feeding followed by one-week of 60% CR in 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 to ICR for MT development with a delay in the MT occurrence. Adiponectin expression in mammary fat pad were significantly higher in CCR group compared to AL. Using GeneChip™ Array, 250 of 3,195 miRNAs were differentially expressed among the dietary groups. 13 of 250 miRNAs were related to adiponectin and/or leptin signaling genes. Results were verified by RT-PCR. Specifically, miR-326-3p, miR-500-3p and miR-129-5p which are adiponectin and/or leptin signaling related 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 Bullets • Type of Calorie restriction 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 adiponectin and/or leptin signaling pathways related genes are regulated by certain miRNAs in the protective effects of CRThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author